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Biomedical subjects

S Heinrich

Publications and source records attributed to S Heinrich.

At least 19 recordsLinked to original sources

Regional chemotherapy in the treatment of advanced pancreatic cancer--is it relevant?

The treatment of pancreatic cancer is still problematic for physicians. Only 15% of patients present with resectable tumours, and systemic chemotherapy is of limited effectiveness. In order to achieve higher local drug concentrations in the tumour without causing the side-effects of a comparable level of systemic treatment, regional chemotherapy has been introduced as an alternative treatment. Several techniques have been developed over recent years, these include: celiac axis infusion (CAI), CAI with microspheres or haemofiltration, aortic stop flow (ASF) and isolated hypoxic perfusion (IHP). Whilst several authors have reported improved response rates and a prolongation of median survival time, these results have not been confirmed by others. In addition, the incidence of side-effects and the rate of technical complications have been reported to be high during regional chemotherapy. Except for a single trial containing 14 patients, no randomised trial comparing systemic and regional chemotherapy has been conducted. For these reasons, none of the reported treatment regimens can be considered to be standard treatment and in order to evaluate, if regional chemotherapy is indeed superior to systemic chemotherapy, randomised trials must be conducted.

Antineoplastic Agents↗

Relevance of locoregional chemotherapy in patients with liver metastases from colorectal primaries.

Progression of colorectal cancer can occur primarily isolated in the liver. But, only the minority of the affected patients is eligible for surgery. Initially, systemic chemotherapy was ineffective in the treatment of unresectable hepatic metastases. For this reason, intraarterial chemotherapy was introduced as treatment alternative to the systemic chemotherapy. Long-term intraarterial chemotherapy regimens with FUDR in patients with colorectal liver metastases, using implantable pumps and ports, resulted in improved response rates, which was confirmed by several randomized trials. However, an improvement in median survival has not yet been demonstrated after regional chemotherapy of hepatic metastases. Since the intraarterial therapy with floxuridine (FUDR) had been reported to result in a high rate of local toxicity, 5-fluorouracil (5-FU) was introduced into regional chemotherapy of the liver. A randomized trial demonstrated superiority of intraarterial 5-FU versus intraarterial FUDR therapy. Despite these reports about high response rates, the benefit of intraarterial chemotherapy remains questionable, because it has not yet resulted in a prolongation of median survival. For this reason, long-term regional chemotherapy cannot be considered as standard treatment and should therefore not be conducted outside controlled clinical trials. Further evaluations on this technique should only be performed in experienced centers.

Antimetabolites, Antineoplastic↗

Fibrosarcoma in infants and children: a retrospective analysis - overdiagnosis in earlier years.

During a 30-year period, 22 patients considered to have a fibrosarcoma (FS) were treated. In a retrospective study the clinicopathologic findings were summarized. With histologic and immunohistochemical re-evaluation, the diagnosis was confirmed in 8 cases. For 6 further patients FS was very probable but specimens were not available. In 8 cases the diagnosis was revised and benign lesions were found in 7. Two patients with irresectable tumors died (infantile FS, FS of mesentery and retroperitoneum). After repeated local recurrences and spread on the affected extremity, an amputation was life-saving in 1 boy. In earlier years many tumors were classified as FSs. Today, immunohistochemistry and molecular-biological methods are valuable tools to clearly identify these tumors. Wide local excision or en-bloc resection without sacrificing any significant function of the part should be the primary form of treatment in infants. Primary re-excision after incomplete excision should have priority over any adjuvant treatment. Preoperative chemotherapy may avoid incomplete resection or mutilation in cases with extended congenital FS.

Child↗

[Technique and pathophysiology of isolated hypoxic perfusion of the abdomen].

Isolated hypoxic perfusion (IHP) is a commonly used technique in the treatment of abdominal malignancies. During a phase II-study the pathophysiology of this technique was explored in patients with advanced pancreatic cancer. Twenty perfusions of the abdomen were performed in 17 patients. Under general anesthesia, femoral vessels were dissected and two balloon catheters were inserted into aorta and vena cava cranial the celiac trunk and the hepatic veins. After instillation of 40 mg of Mitomycin C (MMC) into the running perfusion system, the perfusion was maintained for further 20 minutes. Blood samples were taken in 5-minute intervals to determine pH value, blood gases as well as concentrations of electrolytes, lactate and MMC in the arterial blood. Simultaneously, blood samples were taken from the perfusion blood via a side-port of the extracorporeal perfusion system. Additionally, perfusion pressures, arterial and central venous pressure, heart rate, and the pressure in the aorta distal the balloon catheter were registered continuously. All 20 perfusions had been undertaken without perioperative mortality. After inflating the balloon catheters, blood pressure and heart rate increased rapidly. Within 5 minutes of perfusion an increase in pCO2 and the concentrations of K+ and lactate in the perfusate were registered, while pH and pO2 decreased. Fifteen minutes after instillation of MMC, concentrations of MMC in arterial and perfusion blood were equal. Twenty-four hours after the perfusion all parameters had returned to normal values. IHP was well feasible in 20 consecutive perfusions without major technical problems. A distinct but tolerable combined acidosis resulted from IHP. Despite the exact positioning and control of the balloon catheters a complete isolation was not possible.

Acid-Base Equilibrium↗

Current role of scapulectomy.

Tumors of the scapula are an unusual clinical challenge. Partial or complete resection of the scapula, with its attached musculoaponeurotic tissue, is a seldom used technique for the treatment of primary bone and soft tissue tumors, as well as selected metastatic involvement of the scapula. Scapulectomy may allow wide margins of resection without amputation. The purpose of this study is to review our recent experience with scapulectomy. This study describes the recent experience with scapulectomy by the Section of Surgical Oncology and the Department of Orthopedics at Louisiana State Medical Center (New Orleans, LA). Between 1994 and 1998, 12 patients (between 16 and 79 years of age) underwent a resection of the scapula. Eleven of these patients had soft tissue tumors; one had a metastasis from a thyroid carcinoma. Six of these patients underwent a scapulectomy as a primary treatment, five for recurrence. Six patients also received postoperative radiation and/or chemotherapy. The follow-up ranged from 6 months to 4 years. There was no mortality or wound infection associated with scapulectomy. All patients had normal hand and wrist function after surgery. Three distant recurrences occurred, with no local or regional failures encountered during the follow-up period. Scapulectomy can result in excellent local tumor control. Whereas some loss of active shoulder motion may occur, hand, wrist and elbow function is preserved. Although maintenance of shoulder function should not take precedence over adequacy of resection, scapulectomy remains an excellent procedure for malignant disease that preserves hand, wrist, and elbow function.

Adolescent↗

Hyperosmotic induction of the mitogen-activated protein kinase phosphatase MKP-1 in H4IIE rat hepatoma cells.

The action of hyperosmotic stress on the MAP kinase phosphatase MKP-1 mRNA expression was studied in H4IIE rat hepatoma cells. Hyperosmotic (405 mosmol/L) challenge of the cells led to a transient expression of MKP-1 mRNA, which was maximal after 6-8 h and disappeared completely after 24 h. Hyperosmotic MKP-1 mRNA induction was preceded by a transient activation of the MAP kinases Erk-1, Erk-2, and JNK-2, which were not prerequisite for MKP-1 mRNA accumulation. However, the hyperosmolarity-induced MKP-1 mRNA expression was sensitive to antioxidants and to inhibition of p38 by SB203580. A reduced sensitivity of Erk-1/Erk-2 to other stimuli was found after prolonged hyperosmotic exposure. The data are consistent with a hyperosmolarity-induced MKP-1 expression via reactive oxygen intermediates and p38, which may participate in the termination of MAP kinase activation and contribute to desensitization of the MAP kinases after prolonged hyperosmotic exposure of the cells.

Animals↗

Isolated hypoxic perfusion with mitomycin C in patients with advanced pancreatic cancer.

AIMS: Chemotherapy as a palliative therapy option for patients with advanced pancreatic cancer remains disappointing. Some authors have recently claimed high response rates and a prolongation of median survival after regional chemotherapy. Isolated perfusion may result in the highest drug concentrations within the target tissue without causing systemic side-effects. An established, commercially available system of isolated hypoxic perfusion (IHP) was therefore evaluated in patients with unresectable or recurrent pancreatic cancer. PATIENTS AND METHODS: IHP was performed in 17 patients with unresectable pancreatic cancer. Five women and 12 men with a median age of 61 years were treated. A 20-min isolated hypoxic perfusion was performed after 40 mg of mitomycin C (MMC) had been instilled into the running perfusion system over 5 min. Tumour response was evaluated by CT-scan 6 weeks after IHP. RESULTS: Twenty perfusions were carried out in 17 patients. Within 10 min of perfusion, the perfusate's PO2 decreased to 13% of the baseline value. Five minutes after the infusion of MMC a local concentration of 15.2 mg/litre was observed. Toxicity-related deaths did not occur. Nausea and vomiting (NCI> or =II: 12 episodes) were the most frequently observed toxicities after IHP. In five patients (29%) a deep vein thrombosis occurred. None of the treated patients responded to the regimen used in this trial. The median survival time after IHP was 4.2 months (range 1.3-21). CONCLUSIONS: The overall rate of side-effects and complications after IHP was high. In spite of some hopeful reports on this treatment in recent years, IHP did not show any benefit in terms of tumour response or median survival. On the basis of these experiences, this procedure should no longer be used as treatment for patients with unresectable or recurrent pancreatic cancer.

Aged↗

Acute clozapine overdose: plasma concentration and outcome.

Clozapine is a tricyclic dibenzodiazepine derivative that is classified as an "atypical neuroleptic" drug for treatment of psychotic diseases. A 19-year-old schizophrenic female, treated with 400 mg clozapine per day, was admitted to the emergency department after ingestion of 5000 mg (50 x 100 mg tablets) of clozapine. Clozapine plasma level 2.5 hours after ingestion was 3.8 microg/ml (normal range 0.2-0.7 microg/ml) and very high in gastric lavage. Contrary to reported cases with such high plasma concentrations the patient suffered only from somnolence with intermittent periods of agitation and a mild anticholinergic syndrome with sinus tachycardia and slight hypotension. After detoxication with gastric lavage and short-term administration of pyridostigmine she remained stable, and 24 hours after ingestion she was transferred to the psychiatric unit without further sequelae. To prevent late-onset complications she was carefully monitored for five days. The clozapine plasma level 24 hours after the first measurement was normal. This case and others reported in the literature confirm that signs and symptoms after clozapine intoxication are variable and that high plasma levels are not lethal in every case.

Adult↗

Extended hemipelvectomy in a Jehovah's Witness with erythropoietin support.

The care of patients refusing blood transfusion who require major ablative surgery for malignancy is a continuing challenge. The use of recombinant human erythropoietin is clearly efficacious in patients with renal disease and may be useful in anemic patients who refuse transfusion. Herein, we report a successful extended hemipelvectomy in a Jehovah's Witness using recombinant human erythropoietin support.

Adult↗

[Isolated hypoxic perfusion with mitomycin C confers no benefit for patients with advanced pancreatic carcinoma].

Since therapy options in the treatment of advanced pancreatic cancer are rare, the present study has investigated whether patients with advanced pancreatic cancer may profit from isolated hypoxic perfusion (IHP) of the abdomen with mitomycin C. None of the 17 treated patients responded to IHP with mitomycin C, and the survival time corresponded to that of untreated patients. On the basis of these results, this procedure should no longer be used as treatment for patients with advanced pancreatic cancer.

Adenocarcinoma↗

Florid reactive periostitis.

An 11-year-old boy developed florid reactive periostitis several years after minor trauma. The symptoms responded initially to antibiotics, but after cessation, rapidly recurred and progressed, requiring a ray amputation to relieve the pain and to achieve a functional hand. The reactive periostitis affected the volar aspect of two adjacent phalanges with sparing of the intervening joint, confirming that this is a reactive process rather than a benign neoplasm.

Biopsy↗

Fibrous cortical defect with bizarre nuclear features.

A femoral neck fibrous cortical defect with typical radiographic features had bizarre nuclear features on histological examination. Recognition of the benign radiographic appearance, similar bizarre features of accompanying macrophages, and paucity of mitoses led us to consider this a pseudoanaplastic ischemic or degenerative change in an old fibrous cortical defect. Because the biological behavior was not known with certainty, we closely followed this case. After 25 months, there has been no recurrence or regrowth. The close cooperation between the pathologist and other disciplines facilitates recognition of these pseudoanaplastic lesions and development of treatment strategies for lesions of unknown or uncertain biological behavior.

Adult↗

Regulation of taurocholate excretion by a hypo-osmolarity-activated signal transduction pathway in rat liver.

BACKGROUND & AIMS: Hypo-osmotic cell swelling increases the capacity of taurocholate excretion into bile in the perfused rat liver. The aim of this study was to clarify the mechanisms linking cell swelling to bile acid secretion. METHODS: The influence of hypo-osmotic cell swelling on intracellular signal transduction and bile acid secretion was studied in isolated rat hepatocytes and the perfused rat liver. RESULTS: In rat livers perfused with hypo-osmotic buffer (225 mOsm/L), the maximum velocity of taurocholate excretion into bile is increased by 135% within 10-20 minutes. To unravel signaling events mediating this effect, the activities of the mitogen-activated protein kinases, extracellular-signal-regulated kinase (Erk)-1 and Erk-2, were measured after hypo-osmotic treatment in cultured rat hepatocytes. A rapid parallel activation of Erk-1 and Erk-2 was observed within 1 minute, which became maximal after 10 minutes and returned to the basal level within 60 minutes. The hypo-osmolarity-induced Erk activation and the increase in bile flow after hypo-osmotic liver perfusion were completely abolished by inhibitors of signal transduction at the level of G proteins and tyrosine kinases but remained unaffected by the inhibition of the protein kinase C. CONCLUSIONS: A G protein-and tyrosine kinase-dependent but protein kinase C-independent activation of mitogen-activated protein kinases is involved in the regulation of taurocholate excretion by liver cell hydration changes.

Animals↗

The role of physical therapy in craniofacial pain disorders: an adjunct to dental pain management.

Treatment of craniofacial pain disorders is often complicated by diverse factors such as acute or chronic trauma and persistent postural changes. In addition, emotional issues and life stress often cloud the recovery process. Physical therapists, with their diverse knowledge base and highly competent treatment skills, can be quite effective in assisting dentists and physicians with management of the many difficult upper quarter and craniofacial pain syndromes. This article reviews the role of myofascial and craniosacral dysfunction, as well as the function of posture, tension, and stress in the development of these syndromes. Additionally, it provides a comprehensive overview of the many evaluative techniques and treatment options that can be provided by today's physical therapists.

Chronic Disease↗

A survey of temocillin sensitivity of strains resistant to newer beta-lactam antibiotics.

The susceptibility of a total of 2014 Gram-negative clinical isolates (except Pseudomonas aeruginosa) to a number of antibiotics, including temocillin, was investigated in 2 geographically distinct areas. Overall, more strains were sensitive to temocillin than to mezlocillin, piperacillin, amoxycillin plus clavulanic acid, cefotaxime, cephazolin, latamoxef (moxalactam), cefoxitin, or netilmicin. Susceptibility to temocillin of multiple-resistant strains was studied.

Bacterial Infections↗

[Chemotherapy of the non-small cell carcinoma of the lung with ifosfamide and cisplatin].

80 patients with inoperable non-small cell bronchial carcinoma were treated, at an interval of 4 weeks between them, with ifosfamide (2 g/m2 on days 1-5) and cisplatin (75 mg/m2, day 1). All diagnoses had been confirmed histologically. The course of 72 patients (36 with squamous carcinoma, 25 with adenocarcinoma, two with alveolar-cell carcinoma and nine with large-cell carcinoma) could be evaluated. There were four complete and 21 partial remissions (response rate 35%). In a further 14 patients temporary arrest of tumor growth was registered. Median survival time of all patients was 8.3 months, for those with complete and partial remission 11.5 months. Patients in whom the tumor progressed lived on average 3.9 months. Age and general state of the patients, as well as histological tumor type, had no influence on the results of treatment. Patients in stage IV lived, at seven months, significantly less long than those with only loco-regional spread (11 months). Main side-effects were vomiting, bone-marrow depression and neuropathy. Urotoxicity was not significant, as a result of treatment with mesna. Remission rate and survival time of these patients corresponded with the results obtained with other cisplatin combinations.

Adenocarcinoma↗

Sleeve resection of the bronchus and pulmonary artery for pulmonary lesions.

The tissue preserving resections for non-small-cell bronchial carcinoma were grouped into 3 main categories: I. bronchoplastic procedures, II. angioplastic procedures, and III. concomitant bronchoplastic and angioplastic procedures, and into the subgroups of standard and extended sleeve resections. The indications were: elderly patients, impaired respiratory reserve, limited tumor growth, and palliative surgery. The analysis of 229 cases yielded follow-up data in 192 cases. The estimated 5-year survival rates were 34% in category I, 19% in II, and 14% in III. The decreasing survival is due to greater tumor burden. The operative mortality rate was 8.9% in category I, and 17% in category III, and therefore comparable with standard or extended pneumonectomy respectively. Surgical techniques and postoperative complications are discussed.

Aged↗

Sleeve resection of the bronchus and the pulmonary artery for pulmonary lesions.

The tissue preserving resections for non-small-cell bronchial carcinoma can be grouped into three main categories: I. bronchoplastic procedures, II. angioplastic procedures, and III. concomitant broncho- and angioplastic procedures, and into the subgroups, standard and extended sleeve resection. The indication are; elderly patients, impaired respiratory reserve, limited tumour growth, and palliative surgery. The analysis of 229 cases yielded follow-up data in 192. The estimated 5 year survival rate was 34 per cent, 19 per cent and 14 per cent in categories I, II and III, respectively. The decrease in survival was due to a greater tumour burden. The operative mortality rate was 8.9 per cent in category I and 17 per cent in category III, such being comparable with standard or extended pneumonectomy, respectively. Surgical techniques and postoperative complications are discussed.

Adult↗