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Biomedical subjects

J Brockmann

Publications and source records attributed to J Brockmann.

At least 19 recordsLinked to original sources

Recurrent complicated colon diverticulitis in renal transplanted patient.

Colon perforation due to diverticulitis is a life-threatening complication in the postoperative course of kidney transplantation. In the immunocompromised patient a diagnosis of diverticulitis is difficult to make. We report a 53-year-old woman being kidney transplanted 14 years ago with known diverticulosis. She was admitted with acute severe pain in the lower left abdomen. Abdominal computed tomography (CT) scan indicated a diagnosis of intestinal abscess in the small pelvis. Laparotomy showed a covered sigma perforation with abscess located in the small pelvis (Hinchey-I). Because of the immunocompromised situation of the patient we performed a Hartmann procedure. Her postoperative course was uneventful. In a 6-month interval the intestinal continuity restoration was performed. Twelve days after discharge the patient was readmitted with reduced renal function and increased infection parameters. During physical examination the abdomen was tender. The patient complained of abdominal pain in the left upper abdomen and additional pain in the left shoulder. An antibiotic therapy using ciprofloxacin was already initiated owing to a urinary tract infection. An abdominal CT scan was performed and indicated an intestinal abscess in the left upper abdomen. Laparotomy showed an abscess involving transverse colon, distal jejunum, and proximal ileum (Hinchey-II). Segmental resection of the left colonic flexure, proximal jejunum, and ileum was performed. The postoperative course was uneventful and the patient was discharged on the 8th postoperative day. The present casuistry emphasizes that the immunocompromised patient can undergo diverticulitis twice, and that primary anastomosis is a feasible option for patients with localized peritonitis due to complicated diverticulitis.

Anastomosis, Surgical↗

Alemtuzumab induction and sirolimus plus mycophenolate mofetil maintenance for CNI and steroid-free kidney transplant immunosuppression.

We performed a pilot study in which 22 kidney recipients (14 LD: 8 DCD) were given alemtuzumab induction (30 mg day 0 and 1), steroids (500 mg mp day 0 and 1, none thereafter), mycophenolate mofetil (MMF) maintenance (500 mg b.i.d) and sirolimus (concentration controlled 8-12 ng/mL). With a mean follow-up of 15.9 months, patient survival is (21/22) 96% and graft survival (19/22) 87%. Acute rejections occurred in (8) 36.3% (two humoral). Of 19 surviving grafts, 18 (95%) remain steroid and 15 (79%) CNI-free. At 1 year, mean creatinine was 1.43 mg/dL. Overall infection rates were low, but 2 patients developed severe acute respiratory distress syndrome (ARDS) at month 3 and 7, respectively, resulting in mortality in one and a graft loss in the other. No cancer or PTLD was observed. Leukopenia was common and MMF dose was reduced or eliminated in 6/22 (27%) patients. The reported higher than expected rate of acute rejection, leukopenia and possible pulmonary toxicity suggests excessive morbidity. Modifications such as an initial period of CNI use should be considered.

Acute Disease↗

Development of a gamma-gamma-perturbed angular correlation one-detector method (1-PAC) for investigation of physico-chemical properties of matter.

A new method of the perturbed angular gamma-gamma-correlation (PAC) measurements was developed using one HPGe detector only (1-PAC). For quantifying the perturbation factor, the ratio R gamma 1 + gamma 2 of the summing peak composed of two cascade gamma-rays (the perturbation-affected parameter) to the summing peak composed of one gamma-ray and one X-ray (the perturbation non-affected parameter) was used. This method was demonstrated for the radionuclides 111In and 111mCd, identifying the chemical status of the radionuclides in aqueous solutions.

Journal Article↗

Primary gastrointestinal non-Hodgkin's lymphoma: I. Anatomic and histologic distribution, clinical features, and survival data of 371 patients registered in the German Multicenter Study GIT NHL 01/92.

PURPOSE: The study was initiated to obtain epidemiologic data and information on anatomic and histologic distribution, clinical features, and treatment results in patients with primary gastrointestinal non-Hodgkin's lymphomas (PGI NHL). PATIENTS AND METHODS: Between October 1992 and November 1996, 371 PGI NHL patients were eligible to evaluate clinical features. Radiotherapy and chemotherapy were stratified according to histologic grading, stage, and whether surgery had been carried out or not. RESULTS: A total of 74.8% patients had gastric NHL (PGL). Within the intestine, the small bowel and the ileocecal region were involved in 8.6% and 7.0% of the cases, respectively. Multiple GI involvement (MGI) was 6.5%. Approximately 90% of the GI NHL were in stages IE/IIE. Aggressive NHL accounted for the majority, with a distinguishable pattern in several sites. Forty percent of PGL were of low-grade mucosa-associated lymphatic tissue type. One third of large-cell lymphomas had low-grade components. Most intestinal NHL were germinal-center lymphomas. The site of origin was prognostic. In gastric and ileocecal lymphoma, event-free (EFS) and overall survival (OS) were significantly higher as compared with the small intestine or MGI (median time of observation, 51 months). In PGL, localized disease was prognostic for EFS and OS. Histologic grade influenced only EFS significantly. Numbers in intestinal lymphomas were too small for subanalyses. CONCLUSION: PGI NHL are heterogeneous diseases. The number of localized PGL allowed for detailed analyses. Larger studies are needed for stages III and IV and for intestinal NHL. A uniform reporting system for PGI NHL, in terms of definitions and histologic and staging classifications, is needed to facilitate comparison of treatment results.

Adolescent↗

Primary gastrointestinal non-Hodgkin's lymphoma: II. Combined surgical and conservative or conservative management only in localized gastric lymphoma--results of the prospective German Multicenter Study GIT NHL 01/92.

PURPOSE: The aim of the study was to obtain data on anatomic and histologic distribution, clinical features, and treatment results of patients with primary gastrointestinal non-Hodgkin's lymphomas, particularly combined surgical and conservative treatment (CSCT) versus conservative treatment (CT) alone for primary gastric lymphoma (PGL) in localized stages. PATIENTS AND METHODS: Whether the treatment included surgery was left to the discretion of each participating center. Radiotherapy (Rx) and chemotherapy were stratified according to histologic grading, stage, and the inclusion or omission of surgery as follows: patients with low-grade PGL were treated with extended-field (EF) Rx (30 Gy). In case of residual tumor after surgery or in case of CT only (in stage IIE after six cycles of cyclophosphamide, vincristine, and prednisone), an additional boost of 10 Gy was given. All patients with high-grade PGL were treated with four (stage IE) or six (stage IIE) cycles of cyclophosphamide, doxorubicin, vincristine, and prednisone followed by EF Rx (stage IE) or involved-field (IF) Rx (stage IIE). Rx dosage corresponded to low-grade NHL. RESULTS: Between October 1992 and November 1996, 106 patients had CT only. The survival rate (SR) after 5 years was 84.4% and was influenced neither by patients' characteristics nor by stage or histologic grade. Seventy-nine patients had CSCT. Their SR was 82.0%. Complete resection of the tumor (R0) was prognostic for the overall survival (P =.0165) as compared with incomplete resection. CONCLUSION: Although the study was not randomized, a stomach-conserving approach may be favored.

Aged↗

Phosphorylation of GRK2 by protein kinase C abolishes its inhibition by calmodulin.

G-protein-coupled receptor kinases (GRKs) are important regulators of G-protein-coupled receptor function. Two members of this family L, GRK2 and GRK5 L, have been shown to be substrates for protein kinase C (PKC). Whereas PKC-mediated phosphorylation results in inhibition of GRK5, it increases the activity of GRK2 toward its substrates probably through increased affinity for receptor-containing membranes. We show here that this increase in activity may be caused by relieving a tonic inhibition of GRK2 by calmodulin. In vitro, GRK2 was preferentially phosphorylated by PKC isoforms alpha, gamma, and delta. Two-dimensional peptide mapping of PKCalpha-phosphorylated GRK2 showed a single site of phosphorylation, which was identified as serine 29 by HPLC-MS. A S29A mutant of GRK2 was not phosphorylated by PKC in vitro and showed no phorbol ester-stimulated phosphorylation when transfected into human embryonic kidney (HEK)293 cells. Serine 29 is located in the calmodulin-binding region of GRK2, and binding of calmodulin to GRK2 results in inhibition of kinase activity. This inhibition was almost completely abolished in vitro when GRK2 was phosphorylated by PKC. These data suggest that calmodulin may be an inhibitor of GRK2 whose effects can be abolished with PKC-mediated phosphorylation of GRK2.

Animals↗

Radiochemical separation of no-carrier-added 177Lu as produced via the 176Yb(n,gamma)177Yb-->177Lu process.

The 176Yb(n,gamma)177Yb-beta(-)-->177Lu process was investigated to provide no-carrier-added (nca) 177Lu. The radiochemical separation of the 177Lu from the macro-amounts of the ytterbium target based on the cementation process, i.e. the selective extraction of Yb by Na(Hg) amalgam from Cl-/CH3COO- electrolytes, followed by a final cation exchange purification. The cementation separation process provides a decontamination factor of Yb(III) of 10(4), the cation exchange purification adding a decontamination factor of > 10(2). The nca 177Lu is available in radiochemically pure form despite the chemical similarity of the lanthanides with 75 +/- 5% overall separation yield within 4-5 h. It can be used to synthesise nca 177Lu labelled radiotherapeuticals.

Chromatography, Ion Exchange↗

Long-term investigations after pyloromyotomy for infantile pyloric stenosis.

Between 1919 and 1941, 71 infants suffering from pyloric hypertrophy were operated on by Ramstedt performing an extramucosal pyloromyotomy. Of these patients, we could identify and investigate 41. Four out of 31 long-term surviving patients have been Billroth II-resected (BII). One of these needed re-resection because of an anastomotic ulcer. None of all the long-term survivors developed a carcinoma. Two patients were treated conservatively because of gastritis and one because of esophagitis. All patients, except the one requiring re-resection and one suffering from maldigestion, were absolutely free of complaints. The average time between operation and re-checking was 57 years. The oldest patient was examined 72 years after the operation.

Adolescent↗

Production and radiochemical separation of the Auger electron emitter 140Nd.

Among the Auger electron emitters, the radiolanthanide 140Nd has some unique nuclear properties with potential for endoradiotherapeutic applications. In the present study, 140Nd was produced via the 140Ce(3He,3n) nuclear process at the FZ Jülich CV28 cyclotron, irradiating CeO2 with 3He particles of 36 MeV primary energy. Yields of about 5 MBq 140Nd per microAh were experimentally obtained. Batch yields of > 100 MBq 140Nd were reached. 140Nd was separated in 75 +/- 5% radiochemical yield using a two-step process, first by extracting the bulk of the target material according to a Ce(IV)/Nd(III) separation, then by final ion exchange purification.

Electrons↗

An assessment of diagnostic procedures preparatory to retroperitoneoscopic removal of adenoma in cases of primary hyperaldosteronism.

The goal of this study was to improve assessment of diagnostic measures for lateral localization of aldosterone-producing adrenal adenomas preparatory to retroperitoneoscopic removal, in view of the fact that this technique allows for only unilateral access. A retrospective study was carried out of the medical records of 64 patients (38 women, 26 men, average age 46.8+/-11.2) who underwent surgery at University Hospital, Münster, between 1969 and 1998. Seventeen of the 64 patients presented with hyperplasia and 47 had adrenal adenoma. In cases of hyperplasia, computerized tomography imaged a false-positive unilateral tumor 10 times, a false-negative 3 times, and a unilateral hyperplasia 1 time (ultrasonography: tumor 2 times, false-negative 3 times; 131I-Iodomethylnorcholesterol scintigraphy: tumor 5 times, false-negative 1 time, correct 1 time). In cases of adenoma, computerized tomography yielded accurate results 40 times, imaged a false-negative 2 times, and indicated the incorrect side 1 time (Ultrasonography: false-negative 12 times, correct side 9 times, incorrect side 1 time; 131I-Iodomethylnorcholesterol scintigraphy: correct side 19 times, false-positive (both sides) 5 times, negative 3 times, incorrect side 2 times). Venous sampling, which was carried out seven times, yielded accurate results six times, and failed technically one time. Venous sampling appears to be the method of choice for preoperative lateral localization. Thus, retroperitoneoscopic treatment of Conn's syndrome should not be carried out unless venous sampling is carried out first.

Adenoma↗

Uptake kinetics of the somatostatin receptor ligand [86Y]DOTA-DPhe1- Tyr3-octreotide ([86Y]SMT487) using positron emission tomography in non-human primates and calculation of radiation doses of the 90Y-labelled analogue.

[90Y]DOTA-DPhe1-Tyr3-octreotide ([90Y]-SMT487) has been suggested as a promising radiotherapeutic agent for somatostatin receptor-expressing tumours. In order to quantify the in vivo parameters of this compound and the radiation doses delivered to healthy organs, the analogue [86Y]DOTA-DPhe1-Tyr3-octreotide was synthesised and its uptake measured in baboons using positron emission tomography (PET). [86Y]DOTA-DPhe1-Tyr3-octreotide was administered at two different peptide concentrations, namely 2 and 100 microg peptide per m2 body surface. The latter concentration corresponded to a radiotherapeutic dose. In a third protocol [86Y]DOTA-DPhe1-Tyr3-octreotide was injected in conjunction with a simultaneous infusion of an amino acid solution that was high in l-lysine in order to lower the renal uptake of radioyttrium. Quantitative whole-body PET scans were recorded to measure the uptake kinetics for kidneys, liver, lung and bone. The individual absolute uptake kinetics were used to calculate the radiation doses for [90Y]DOTA-DPhe1-Tyr3-octreotide according to the MIRD recommendations extrapolated to a 70-kg human. The highest radiation dose was received by the kidneys, with 2.1-3.3 mGy per MBq [90Y]DOTA-DPhe1-Tyr3-octreotide injected. For the 100 microg/m2 SMT487 protocol with amino acid co-infusion this dose was about 20%-40% lower than for the other two treatment protocols. The liver and the red bone marrow received doses ranging from 0.32 to 0.53 mGy and 0.03 to 0.07 mGy per MBq [90Y]DOTA-DPhe1-Tyr3-octreotide, respectively. The average effective dose equivalent amounted to 0. 23-0.32 mSv/MBq. The comparatively low estimated radiation doses to normal organs support the initiation of clinical phase I trials with [90Y]DOTA-DPhe1-Tyr3-octreotide in patients with somatostatin receptor-expressing tumours.

Anesthesia↗

PET-pharmacokinetics of 18F-octreotide: a comparison with 67Ga-DFO- and 86Y-DTPA-octreotide.

The quantitative uptake kinetics of (2-[18F]fluoropropionyl-(D)phe1)-octreotide (I), a somatostatin (SRIF) receptor-specific tracer, was measured by PET. Conventional organ biodistribution and in vivo stabilities of the tracer as well as in vivo displacement and SRIF receptor blocking were determined. The 18F-fluorinated octreotide was compared with ([67Ga]-DFO-B-succinyl-(D)phe1)-octreotide (II) and ([86Y]-DTPA-(D)phe1)-octreotide (III). Initially, 2-10 MBq of the labeled tracers were injected into male Lewis rats bearing an exocrine pancreatic islet cell tumor. PET measurements were performed dynamically between 0 and 120 min postinjection. Organ distributions were determined 5, 15, 30, 60, and 120 min postinjection. The extent of metabolic degradation was analyzed in serial blood and urine samples as well as in homogenized samples of tumor, liver, and kidney. The uptake of (I) by the tumor was rapid (maximum accumulation at 1-2 min postinjection) and high (about 0.5 +/- 0.2% ID/g), followed by a fast and continuous release with koff = 10 +/- 2. 10(-5) s-1. The tracer was found to remain intact in vivo up to 120 min postinjection. Specific binding of (I) to SRIF receptors in the adrenals, the pancreas, and the pituitary gland was demonstrated in vivo by pretreatment and displacement experiments. Compound (II) also showed a fast uptake by the tumor. Its tumor residence half-life was longer (koff = 3.0 +/- 0.5 . 10(-5) s-1). Compound (II) was also predominantly excreted intact. One hour postinjection, the remaining activity in the blood pool was found to be bound to serum proteins. Early uptake kinetics for compound (III) were also rapid but reached only half the tumor uptake of (II). Compared to (I), the release of 86Y-activity from the tumor was slower (koff = 3.1 +/- 1.3 . 10(-5) s-1). Compared to (II), compound (III) was considerably less stable in vivo. The main critical organs for (II) and (III) are kidneys and bones, whereas (I) is predominantly accumulated in the liver. The in vivo behavior of (I) closely resembles 14C-labeled octreotide. Thus, 18F-labeled octreotide may be of interest in the quantitation and investigation of in vivo properties of somatostatin receptors by PET. However, the short residence of (2-[18F]fluoropropionyl-(D)phe1)-octreotide in tumors and its hepatobiliary excretion may complicate the interpretation of abdominal tumors.

Animals↗

[Injuries of the extrahepatic bile ducts. Clinical aspects, diagnosis and therapy].

From 1990 to 1995, 27 patients with biliary injuries were treated at the Department of General Surgery of Münster University Hospitals. All lesions occurred during cholecystectomy, either via laparoscopy (n = 17) or via laparotomy (n = 10). Ten patients were male and 17 female. The mean age was 51.2 years. In all cases a preoperative ERCP was performed. Based on the ERCP status a new classification was developed taking into account the type and location of the injury, as well as the opportunity for endoscopic treatment. Twenty-two patients underwent surgical bile duct reconstructions (12 hepaticojejunostomies, 3 choledochojejunostomies, 7 direct reconstructions). In five cases endoscopic therapy alone was successful. The perioperative mortality was 7.4% (2/27). Three of the surviving 25 had to be readmitted for recurrent cholangitis. Only 15 feel well without any limitations on everyday activities.

Bile Ducts, Extrahepatic↗

[Surgical procedure in non-Hodgkin's lymphomas of the digestive system--a status quo analysis].

A total of 329 patients were registered in the Münster multicenter study, "Gastrointestinal Lymphomas", including 118 different centers since October 1992. Primary surgical intervention was performed in 135 cases. In contradiction to the prospective results of other oncological centers, the preoperative diagnosis of non-Hodgkin lymphoma was only known in 44.4% of cases. R0 resection was achieved in only 62 of the 135 patients (46%). This study reveals the realistic situation of operative treatment of non-Hodgkin lymphomas in everyday practice.

Gastrointestinal Neoplasms↗