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Biomedical subjects

D Lorenz

Publications and source records attributed to D Lorenz.

At least 19 recordsLinked to original sources

No benefit of 3,4-diaminopyridine in essential tremor: a placebo-controlled crossover study.

3,4-Diaminopyridine (3,4-DAP) is a potassium channel blocker that has recently demonstrated an antioscillatory effect in humans by significantly reducing downbeat nystagmus. Based on the presumed role of intrinsic oscillations in the pathophysiology of essential tremor (ET), the authors conducted a double-blind, placebo-controlled crossover study assessing the antitremor effect of a single dose of 3,4-DAP in 19 patients with ET. They did not find any significant change in tremor severity as measured by clinical ratings or accelerometry.

4-Aminopyridine↗

High-dose rituximab and anti-MAG-associated polyneuropathy.

Rituximab has been administered successfully in patients with polyneuropathy associated with antibodies to myelin-associated glycoprotein (anti-MAG). The authors present a follow-up study with high-dose rituximab. Increase of rituximab from 375 mg/m2 to a dose of 750 mg/m2 was well tolerated and led to clinical improvement in four of eight patients, along with improvement of nerve conduction velocities and a reduction of anti-MAG antibody titers.

Aged↗

Spontaneous splenic rupture, in tertian malaria.

We report a case of tertian malaria in a 36-year-old Caucasian male complicated by spontaneous splenic rupture 2 months after returning from Kenya. The ruptured and enlarged spleen displaying multiple subcapsular hemorrhages was surgically resected. Histological examination revealed a marked enlargement of the red pulp and a reduced white pulp in addition to hyperemia of the spleen. Tertian malaria was diagnosed by peripheral blood smear and elevated antibody titer against Plasmodium vivax. The patient underwent antimalarial therapy with chloroquine and primaquine and the further course was uneventful. Etiopathology, differential diagnosis and therapy of this rare complication in malaria are discussed.

Adult↗

High concordance for essential tremor in monozygotic twins of old age.

OBJECTIVE: To assess the relative contribution of genetic and environmental factors for the etiology of essential tremor (ET) and to explore the effect of different diagnostic criteria. METHODS: A total of 2,448 twins of the Danish twin registry aged 70 years or more were screened for ET by an interview and an Archimedes spiral test. All twin pairs (n = 162) with a positive screening test of at least one of the twins were recontacted and 218 individuals (109 pairs) were interviewed and examined by a movement disorder specialist. The consensus criteria of the Tremor Investigation Group were applied to diagnose ET. RESULTS: Twenty-nine twins fulfilled the criteria of definite, 7 of probable, and 56 of possible ET. The probandwise concordance rate for the broadest definition of ET was 77% for monozygotic twins (MZ) and 59% for dizygotic twins (DZ). However, in an analysis restricted to cases of probable and definite ET, the concordance rates were 93% and 29%. The heritability for the liability to ET ranged from 93% to 99% using a general population prevalence of 1.2% for white 70+-year-olds. The inclusion of probable and exclusion of possible cases in the diagnosis of ET produced the highest concordance rates. CONCLUSION: The high concordance among MZ twins of very old age in this first population-based twin study of ET suggests that a disease phenotype consisting of definite and probable ET has a high heritability and hence is a good candidate for a phenotype to be used in linkage studies.

Age Factors↗

Randomized clinical trial of lightweight composite mesh for Lichtenstein inguinal hernia repair.

BACKGROUND: Almost half the patients who undergo hernia repair with mesh report a feeling of stiffness and a foreign body in the groin. This study evaluated whether patients noticed any difference between lightweight and standard polypropylene mesh for the repair of inguinal hernia. METHODS: Patients scheduled for elective repair of unilateral or bilateral, primary or recurrent inguinal hernia by the Lichtenstein technique were randomized to receive either a conventional densely woven polypropylene mesh (100-110 g/m(2)) or a lightweight composite multifilament mesh (polypropylene 27-30 g/m(2)). Quality of life was assessed using Short Form 36 before operation and 6 months after surgery. Pain was assessed by means of a visual analogue scale 2 days and 6 months after surgery. The primary outcome measure was the feeling of a foreign body in the groin at 6 months. RESULTS: Some 122 hernias were randomized; 117 were included in the analysis of perioperative data, and 106 were re-examined after 6 months. There were no differences between the treatment groups with respect to early and late surgical complications. Use of lightweight mesh was associated with significantly less pain on exercise after 6 months (P = 0.042). In addition, fewer patients reported the feeling of a foreign body after repair with lightweight mesh (17.2 versus 43.8 per cent with conventional mesh; P = 0.003). Quality of life was improved significantly at 6 months compared with the preoperative assessment, and there were no differences between the treatment groups. CONCLUSION: Lightweight polypropylene mesh may be preferable for Lichtenstein repair of inguinal hernia. Larger cohorts with longer follow-up are needed before it can be recommended for routine use.

Adult↗

Gait analysis of sporadic and hereditary spastic paraplegia.

OBJECTIVES: Sporadic (SSP) and hereditary spastic paraplegias (HSP) are clinically and genetically heterogeneous disorders, which are characterised by a slowly progressive spastic paraparesis. Initial symptoms and the rate of progression are variable even among members of the same family. Spastic paraparesis is the major and most disabling clinical symptom and was assessed with gait analysis using a three-dimensional infrared movement analysis system. METHODS AND RESULTS: 22 patients with clinically and/or genetically confirmed SSP/HSP were compared with age-matched control subjects. Significantly lower values were found for gait velocity, stride length, step height and the range of motion of the knee-angle. The gait pattern is characterised by a severe spasticity of both legs with only mild paresis. The balance-related gait parameters show a broad-based gait without inwardly rotated feet. No correlation was found between disease duration and the severity of the gait disorder and the central motor conduction time to the leg muscles and the abnormal gait parameters. The gait pattern did not differ between the 7 SSP cases and the 15 HSP cases. CONCLUSIONS: We conclude that three-dimensional gait analysis can uncover specific features of such rare gait disorders, and may be used as an objective tool to quantify the impairment of gait parameters in patients with SSP/HSP and thus can be used to monitor disease progression and the effect of therapeutic interventions.

Adult↗

[The Rapunzel syndrome: rare manifestation of a trichobezoar of the upper gastrointestinal tract].

The Rapunzel syndrome is a rare manifestation of a gastric trichobezoar with a "tail" extending throughout the small intestine and sometimes even to the colon. We report on the surgical removal of such a bezoar in a 4-year-old patient by gastrotomy--the third published case in the German literature. The syndrome is mainly seen in young girls with trichophagia psychodynamically associated with early childhood deprivation and a high comorbidity of serious pediatric psychiatric disorders. The symptoms are nonspecific and may mimic those of other pathologic gastrointestinal conditions. Clinical characteristics are a movable mass in the epigastrium and alopecia. The therapy of choice is surgery of the trichobezoar together with the whole intestinal "tail," as in most cases endoscopic removal fails due to the large extension. Early diagnosis and treatment of the Rapunzel syndrome is of eminent importance in order to avoid later fatal complications such as gastric perforation and intestinal necroses. Intensive psychiatric follow-up is mandatory for preventing relapses.

Alopecia Areata↗

Contribution of intraoperative cholangiography to incidence and outcome of common bile duct injuries during laparoscopic cholecystectomy.

BACKGROUND: In the present study we examined, in a meta-analysis of the literature, the contribution of intraoperative cholangiography (IOC) to incidence, type, and time of diagnosis of common bile duct (CBD) injuries during laparoscopic cholecystectomy (LC). MATERIALS AND METHODS: Forty of 2104 reports were enrolled for analysis. In 26 reports we found exact information on type, location and repair of 405 major injuries and in a subgroup examination we selected 103 major injuries with detailed information as to the event and size of CBD injury in association with IOC. RESULTS: The main incidence of CBD injuries was 0.36%. Using the method of routine IOC the incidence was 0.21% and the rate of diagnosis at the time of cholecystectomy 87% in contrast to selective use of IOC with 0.43% and 44.5%. In 405 cases of major CBD injuries, severe injuries predominated in 83.9% of the cases. Reconstruction with the help of a bilio-digestive anastomosis was necessary in 45.7% of all patients. In 34.8% of the cases a second intervention had to be made in the follow-up of 4 years after LC. The analysis of type, severity, recognition, and follow-up of CBD injuries during LC w/wo IOC showed significant advantages for doing routine IOC. CONCLUSIONS: The use of IOC can avoid severe types of CBD injuries during LC, increase the recognition at the time operation, and influence the success of repair and outcome of the patients.

Anastomosis, Surgical↗

Evaluation of healthcare utilization and health status of patients with Parkinson's disease treated with deep brain stimulation of the subthalamic nucleus.

OBJECTIVE: To assess the effects on motor functioning, health status and direct medical costs of high-frequency stimulation of the subthalamic nucleus (DBS-STN) in patients with idiopathic Parkinson's disease (PD). In addition, the cost-effectiveness of DBS-STN vs. drug treatment was investigated. METHODS: 16 consecutive patients with PD from two centers (Düsseldorf/Cologne; Kiel) treated by DBS-STN were prospectively evaluated. Clinical evaluations were done at baseline and 1, 3, 6, 12 months following surgery by means of the Unified Parkinson's disease Rating Scale (UPDRS). Health status of PD patients was assessed using the Sickness Impact Profile (SIP) at baseline and 6 months following surgery. Relevant economic data were taken from the medical records and costs (1999) were derived from different German medical economic resources. Costs were determined from the perspective of the health care provider. RESULTS: Following DBS-STN UPDRS scores (subscores and sum score) as well as health status improved considerably in PD patients. The overall SIP score and the physical dimension score (p < 0.009) were significantly different (p < 0.01) six month after surgery compared with baseline values. Mean costs of DM 40,020 (US dollars 20,810, EURO 20,410, GB pounds 12,810) per patient were spent during the 12 month observation period for in-patient and out-patient care. These expenses included already the costs for the electronic device for bilateral stimulation. Following DBS-STN medication was considerably reduced. Mean daily drug costs at baseline were DM 46.7+/-21.8 (US dollars 24, EURO 24, GB pounds 15) and DM 18.3+/-17.7 (US dollars 10, EURO 9, GB pounds 6) at 12 months following DBS-STN. Accounting for the decreased drug consumption, total annual costs amounted to DM 31,400 (US dollars 16,330, EURO 16,010, GB pounds 10,050). Further, we estimated the incremental cost effectiveness as DBS-STN had higher costs but was more effective than baseline treatment. The incremental total cost-effectiveness ratio for DBS-STN was DM 1.800 (US dollars 940, EURO 920, GB pounds 580) for one point decrease of the UPDRS. CONCLUSION: DBS-STN is an effective treatment that considerably alleviates the severity of signs and symptoms and improves the health status of patients with PD. Compared with drug treatment, however, the expenditures associated with DBS-STN are increased when only direct medical costs are considered in a one year horizon. However, on a long-term basis costs will decrease considerably because of the reduction of the drug expenditure and improved functioning in all activities of daily living. To adequately evaluate the cost-effectiveness of DBS-STN compared with standard drug regimen for PD it is necessary to include direct, indirect and intangible costs on a long-term basis and under standardized circumstances.

Aged↗

[Diagnostic and therapeutic management of symptomatic cholecystolithiasis and pre-operatively suspected choledocholithiasis].

The goal of this study was to examine the effectiveness of endoscopic retrograde choledocho-pancreatography (ERCP) at the Unfallkrankenhaus Berlin in the setting of pre-operative suspicion of choledocholithiasis. The predictive value of various pathologic findings with regard to choledocholithiasis was to be determined in this patient population.All patients treated operatively for symptomatic cholecystolithiasis between August 2000 and August 2001 were evaluated retrospectively for the following variables: age, gender, operative strategy, intra-operative cholangiography, sonographic findings, occurrence of choledocholithiasis. In 21.4 % of 196 patients who underwent cholecystectomy (n = 42) a pre-operative ERCP was performed. In 19 of these 42 patients, no pathology was found on ERCP. The percentage of therapeutic pre-operative investigations was 47.6 % (n = 20). In 3 patients, a juxtapapillary diverticulum was seen.69.9 % of the operations (n = 137) were performed laparoscopically. 167 patients (85.2 %) underwent intra-operative cholangiography. In 4 patients, the ERCP was performed post-operatively. The indication for 3 of those 4 examinations was an abnormal intra-operative cholangiogram. Complications occurred in 4 of the 46 patients who underwent ERCP (8.7 %). Choledocholithiasis was found in 12.2 % (n = 24) of all 196 patients. The pathologic finding with the highest positive predictive value for the diagnosis of choledocholithiasis was the finding of a dilated common bile duct to more than 8 mm diameter (PPV 75 %). Among laboratory variables investigated in this study, the elevation of serum bilirubin level exhibited the highest positive predictive value (PPV 39.2 %).

Adolescent↗

Effects of bilateral subthalamic nucleus stimulation on parkinsonian gait.

Gait analysis was carried out to assess the effects of L-dopa and bilateral subthalamic nucleus stimulation on gait velocity, cadence, stride length, and gait kinematics in nine patients with PD. Substantial effects of bilateral subthalamic nucleus stimulation on gait, with an increase in gait velocity and stride length comparable to that of a suprathreshold L-dopa dose, were found. Interestingly, stride length was more improved by L-dopa and cadence more by subthalamic nucleus stimulation. In two patients with freezing during the "on" period, subthalamic nucleus stimulation failed to reduce this symptom effectively.

Antiparkinson Agents↗

Role of a JAK3-dependent biochemical signaling pathway in platelet activation and aggregation.

Here we provide experimental evidence that identifies JAK3 as one of the regulators of platelet function. Treatment of platelets with thrombin induced tyrosine phosphorylation of the JAK3 target substrates STAT1 and STAT3. Platelets from JAK3-deficient mice displayed a decrease in tyrosine phosphorylation of STAT1 and STAT3. In accordance with these data, pretreatment of human platelets with the JAK3 inhibitor WHI-P131 markedly decreased the base-line enzymatic activity of constitutively active JAK3 and abolished the thrombin-induced tyrosine phosphorylation of STAT1 and STAT3. Following thrombin stimulation, WHI-P131-treated platelets did not undergo shape changes indicative of activation such as pseudopod formation. WHI-P131 inhibited thrombin-induced degranulation/serotonin release as well as platelet aggregation. Highly effective platelet inhibitory plasma concentrations of WHI-P131 were achieved in mice without toxicity. WHI-P131 prolonged the bleeding time of mice in a dose-dependent manner and improved event-free survival in a mouse model of thromboplastin-induced generalized and invariably fatal thromboembolism. To our knowledge, WHI-P131 is the first anti-thrombotic agent that prevents platelet aggregation by inhibiting JAK3.

Animals↗

An inhibitory role of Rho in the vasopressin-mediated translocation of aquaporin-2 into cell membranes of renal principal cells.

Vasopressin regulates water reabsorption in renal collecting duct principal cells by a cAMP-dependent translocation of the water channel aquaporin-2 (AQP2) from intracellular vesicles into the cell membrane. In the present work primary cultured inner medullary collecting duct cells were used to study the role of the proteins of the Rho family in the translocation of AQP2. Clostridium difficile toxin B, which inhibits all members of the Rho family, Clostridium limosum C3 toxin, which inactivates only Rho, and the Rho kinase inhibitor, Y-27632, induced both depolymerization of actin stress fibers and AQP2 translocation in the absence of vasopressin. The data suggest an inhibitory role of Rho in this process, whereby constitutive membrane localization is prevented in resting cells. Expression of constitutively active RhoA induced formation of actin stress fibers and abolished AQP2 translocation in response to elevation of intracellular cAMP, confirming the inhibitory role of Rho. Cytochalasin D induced both depolymerization of the F-actin cytoskeleton and AQP2 translocation, indicating that depolymerization of F-actin is sufficient to induce AQP2 translocation. Thus Rho is likely to control the intracellular localization of AQP2 via regulation of the F-actin cytoskeleton.

Amides↗

[Surgical therapy in cholecysto-/choledocholithiasis. Results of a Germany-wide questionnaire sent to 859 clinics with 123,090 cases of cholecystectomy].

BACKGROUND: With the advent of laparoscopic cholecystectomy, the choice of procedure (laparoscopic vs open) and surgical management in gallstone disease are of interest. The purpose of this study was to examine the current approach and various strategies for cholecystectomy in Germany. METHODS: A retrospective survey at 859 (of 1,200, 67.6%) hospitals in Germany was conducted. Data from 123,090 patients that had undergone cholecystectomy were analyzed. RESULTS: 71.9% of the procedures were finished laparoscopically (LC: 88.537), whereas 22.5% (27.727) were done in the open technique (KC). Conversion to open surgery was required in 7.1% of the laparoscopically started operations, mainly in cases of adhesions and unclear anatomic situations (64.3%). When common bile duct (CBD) stones were diagnosed preoperatively, 74.4% of the participants favored primary endoscopic extraction (ERC), followed by LC. In cases of intraoperative diagnoses, the LC was finished and postoperative ERC and extraction were carried out in more than half of the hospitals (58.4%). Sixteen percent were converted to an open operation with simultaneous exploration of the CBD. Laparoscopic desobstruction of the CBD was extremely rare (4.4%). The intraoperative cholangiography (IOC) was the most strongly recommended approach for intraoperative diagnostics, but was generally routine practice in only 6% of the hospitals conducting LCs. Forty-nine percent of the respondents reported the use of IOC in selected cases and 43% of the hospitals did not perform any intraoperative diagnostics in LC. Compared with OC, the results show a lower incidence of postoperative reinterventions (0.9 vs 1.8%) and fatal outcomes (0.04 vs 0.53%) for LC. In contrast, CBD injuries were more frequent in the LC group (0.32 vs 0.12%). The median duration of hospitalization was 6.1 days (range 2.8-12) in the LC group compared with 10.4 days (range 3-28) in the OC group. CONCLUSIONS: LC is the standard procedure for the treatment of uncomplicated gallstone disease. Even after adjustment for differences in patient comorbidities, there are logical differences between the hospitals as to the type of cholecystectomy used for acute cholecystitis, the management of CBD stones, and the intraoperative diagnostics in LC.

Cholangiography↗

[Hand-assisted, laparoscopic nephrectomy for live donor organ harvesting. Initial results].

We report technique and preliminary results with a new, laparoscopic hand-assisted, technique for live donor nephrectomy. A special device (Pneumo-Sleeve, Handport) in a short (7.5-8 cm) Pfannenstiel incision allows the surgeon to insert his or her hand into the insufflated abdominal cavity and to use it as a "multifunctional instrument" while pneumoperitoneum is preserved. This technique offers significant advantages over the pure laparoscopic approach in terms of maintained tactile feedback, facilitated exposure and dissection, decreased operation time and easy retrieval of specimen with minimized allograft warm ischemia time.

Female↗

Cell volume kinetics of adherent epithelial cells measured by laser scanning reflection microscopy: determination of water permeability changes of renal principal cells.

The water channel aquaporin-2 (AQP2), a key component of the antidiuretic machinery in the kidney, is rapidly regulated by the antidiuretic hormone vasopressin. The hormone exerts its action by inducing a translocation of AQP2 from intracellular vesicles to the cell membrane. This step requires the elevation of intracellular cyclic AMP. We describe here a new method, laser scanning reflection microscopy (LSRM), suitable for determining cellular osmotic water permeability coefficient changes in primary cultured inner medullary collecting duct (IMCD) cells. The recording of vertical-reflection-mode x-z-scan section areas of unstained, living IMCD cells proved useful and valid for the investigation of osmotic water permeability changes. The time-dependent increases of reflection-mode x-z-scan section areas of swelling cells were fitted to a single-exponential equation. The analysis of the time constants of these processes indicates a twofold increase in osmotic water permeability of IMCD cells after treatment of the cells both with forskolin, a cyclic AMP-elevating agent, and with Clostridium difficile toxin B, an inhibitor of Rho proteins that leads to depolymerization of F-actin-containing stress fibers. This indicates that both agents lead to the functional insertion of AQP2 into the cell membrane. Thus, we have established a new functional assay for the study of the regulation of the water permeability at the cellular level.

Actins↗