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M Schatz

Publications and source records attributed to M Schatz.

At least 37 records · Page 2Linked to original sources
PubMed1999

Basic research supported developments of chemotherapy in nonresectable isolated colorectal liver metastases to a protocol of hepatic artery infusion using mitoxantrone, 5-FU + folinic acid and mitomycin C.

OBJECTIVE: Since the developments in systemic chemotherapy of metastasized colorectal cancer have not resulted in substantial gains in survival times, we wished to improve the course of isolated nonresectable colorectal liver metastases (CPLM) by hepatic arterial infusion treatment. BACKGROUND: Patients (pts) with CRLM have a worse fate than those pts whose liver metastases could be resected. Systemic (i.v.) chemotherapy for CRLM/colorectal metastases does not improve survival to a relevant level (median survival time (med. surv.) after 5-Fluorouracil + Folinic Acid (5-FU + FA) i.v.: 6.4-14.3 months (m)). Hepatic artery infusion (HAI) with 5-Fluorode-oxyuridine (5-FUDR) has been demonstrated in a metaanalysis of randomized trials to be superior to i.v. treatment/palliative care (med. surv.: 15 vs. 10 m). The benefit of HAI with 5-FUDR, although recommended as treatment for CRLM, is severely compromised by the 5-FUDR induced hepatotoxicity, leading eventually to sclerosing cholangitis (SC)/liver scirrhosis. We have stepwise developed a protocol for HAI of CRLM, which is superior to HAI with 5-FUDR, and, most evidently, to systemic chemotherapy. PATIENTS/METHODS: Between 1982-1997, 222 CR (L) M patients were treated within subsequent protocols (Table). In protocol A, 68 CRLM pts received HAI with 5-FUDR (A1: nonrandomized pts; A2: randomized pts). In protocol B (randomized pts.), 46 pts received 5-FUDR i.a. (via HAI) + i.v. In protocol C, systemic chemotherapy with 5-FU + FA was conducted in 34 pts with metastasized colorectal cancers, including CRLM. In protocol D 5-FU + FA was delivered via HAI in 25 pts with CRLM. In protocol E, based on in vitro phase II studies and the results of protocol D, Mitoxantrone and Mitomycin C were added to 5-FU + FA (MFFM). Fifty (50) CRLM pts received HAI with MFFM. RESULTS: The response rates, med. surv. times, systemic toxicity and SC rates are shown in the table. HAI with MFFM produced objective responses in 66%, the med. surv. was 27.4 m, and no SC occurred. The ports surgically placed for HAI, e.g., in protocols D and E, functioned in 90%, 82%, and 76% 6, 9, and 11 m after start of the HAI. Quality of life in protocol E was high. Nine pts from protocols D + E with either partial (PR, 7 pts) or complete (CR, 2 pts) remissions received a secondary liver resection without hospital mortality, and 7/9 pts are living 2-58 m after liver resection, 2/9 pts died 11 and 22 m after resection. [table: see text] SUMMARY/CONCLUSIONS: Our learning curve to achieve optimal treatment of CRLM resulted in a protocol using HAI with MFFM. The results of this protocol (E) including the high remission rate, long median survival time, good port function, high quality of life, and, most interestingly, the possibility to downstage and resect primarily nonresectable metastases, seem to be superior to HAI with 5-FUDR of 5-FU + FA and to systemic chemotherapy with 5-FU + FA. This hypothesis is currently examined in a phase III study (HAI with MFFM vs. 5-FU + FA i.v.).

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1999

Surgery and multimodal treatments in pancreatic cancer--a review on the basis of future multimodal treatment concepts.

BACKGROUND: To improve the surgical outcome after resection of pancreatic adenocarcinomas, multimodal treatment concepts need to be applied and improved. In spite of several positive studies, and the fact that multimodality treatment is the standard concept in major centers for pancreatic cancer surgery, a recent trial shed some doubt on the positive effect of adjuvant radiochemotherapy, so that the majority with reservations about multimodal treatment feel confirmed in their opinion that surgical treatment alone is sufficient therapy for resectable pancreatic cancer. The controversy among those for and against adjuvant treatment need an up-to-date review of the indications and results achievable with various treatment modalities. PATIENTS/METHODS: The literature on the indications and results of adjuvant/neoadjuvant therapies in pancreatic cancer was reviewed to provide a solid base for current recommendations and future developments. A special view was concentrated on the biology of the disease in the spontaneous course, after surgery and during/after various palliative and adjuvant/neoadjuvant treatment modalities, to characterize the disease for an optimally targeted treatment in conjunction with surgical removal of the tumor. The results of systemic and regional chemotherapy and radiotherapy either alone or in combination, before, during, and after surgery, were critically analyzed with respect to the oncological possibilities and pitfalls of each treatment method. RESULTS: In two randomized trials, one testing postoperative radiochemotherapy (GITSG), and one postoperative chemotherapy (Bakkevold), the adjuvant treatment achieved a significant prolongation of the median survival time. The 5- and 10-year survival rates were improved in the GITSG study. The EORTC-GITCCG trial could not confirm the benefit of adjuvant radiochemotherapy. This study had a different design than the GITSG trial. Several historical control studies supported the beneficial effect of postoperative radiochemotherapy. In three historical control trials using regional chemotherapy, one with intraoperative radiotherapy, the survival times were improved vs. surgery alone. Intraoperative or postoperative radiotherapy as single modalities might reduce local relapses, but a survival advantage is still debated. Preoperative neoadjuvant radiochemotherapy has several advantages (downstaging, devitalizing margins and lymph node metastases, compatibility of treatment vs. postoperative radiochemotherapy), and does not seem to increase the postoperative morbidity. Several trials have confirmed the feasibility of this concept, but no survival advantage has yet been proven. Systemic and regional chemotherapy is able to downstage primarily nonresectable pancreatic cancers. CONCLUSIONS: Postoperative adjuvant radiochemotherapy with up-to-date protocols can be recommended for routine treatment, if the surgeon or the patient desires to improve the usually remote prognosis after surgery alone. For those being undecisive or against adjuvant therapy, the participation in trials, e.g., ESPAC 1 and 2 studies, is strongly recommended. Regarding our own positive experience with adjuvant regional chemotherapy and in view of the postresectional progression pattern, we currently favour adjuvant radiochemotherapy, with the chemotherapy delivered regionally via the celiac axis. This concept will be tested vs. surgery alone in the ESPAC 2 trial. Neoadjuvant therapies have a great potential, but should be conducted within studies, such as pre-, intra-, or postoperative radiotherapy.

Adenocarcinoma↗
PubMed1998

The 80S rat liver ribosome at 25 A resolution by electron cryomicroscopy and angular reconstitution.

BACKGROUND: The ribosome is central to protein synthesis in all living organisms. Single-particle electron cryomicroscopy has recently led to the determination of three-dimensional structures of bacterial ribosomes to approximately 20 A, which have since revolutionised our understanding of ribosomal function. The structure we present here of the 80S rat liver ribosome leads the way to similar progress for mammalian ribosomes. RESULTS: Among the new details revealed by our 25 A structure of the 80S rat liver ribosome are channels within the subunits, a large 'flat ribosomal surface' (FRS) on the outer surface of the large subunit and structural extensions of the mammalian compared to the bacterial ribosome. The main large subunit channel in both the bacterial and the mammalian species starts at the peptidyl transferase centre, below the central protuberance, and ends in the FRS, at the lower back of the large subunit. Structurally, the channels of both species can be directly superimposed. CONCLUSIONS: The mammalian structural extensions--none of which trespass the FRS--can be interpreted in terms of rRNA inserts and additional protein content over that of bacterial ribosomes. The main large subunit channel, which ends at the FRS, is the best candidate for the exit channel for proteins targeted for the endoplasmic reticulum.

Animals↗
PubMed1998

Resection and radiochemotherapy of pancreatic cancer--the future?

BACKGROUND: To improve the surgical outcome after resection of pancreatic adenocarcinomas, multimodal treatment concepts need to be applied and improved. The controversies among those being pro and contra adjuvant treatment need an up-to-date review of the indications and results achievable with various treatment modalities. PATIENTS/METHODS: The literature regarding the indications and results of adjuvant/neoadjuvant therapies in pancreatic cancer was reviewed to provide a solid base for current recommendations and future developments. The biology of the disease in the spontaneous course, after surgery and during/after various palliative and adjuvant/neoadjuvant treatment modalities was focussed on, to characterise the disease for an optimally targeted treatment in conjunction with surgical removal of the tumour. The results of systemic and regional chemotherapy and radiotherapy, either alone or in combination, before, during and after surgery were critically analysed with respect to the oncological possibilities and pitfalls of each treatment method. RESULTS: In two randomised trials, one testing postoperative radiochemotherapy (GITSG), and one postoperative chemotherapy, the adjuvant treatment achieved a significant prolongation of the median survival time. The 5-year and 10-year survival rates were improved in the GITSG study. The EORTC-GITCCG trial could not confirm the benefit of adjuvant radiochemotherapy. This study had a different design than the GITSG trial. Several historical control studies supported the beneficial effect of postoperative radiochemotherapy. In three historical control trials using regional chemotherapy, one with intraoperative radiotherapy, the survival times were improved compared with surgery alone. Intraoperative or postoperative radiotherapy as single modalities might reduce local relapses, but a survival advantage is still debated. Preoperative neoadjuvant radiochemotherapy has several advantages (downstaging, devitalising margins and lymph node metastases, compatibility of treatment vs. postoperative radiochemotherapy), and does not seem to increase the postoperative morbidity. Several trials have confirmed the feasibility of this concept, but no survival advantage has yet been proven. Systemic and regional chemotherapy is able to downstage primarily nonresectable pancreatic cancers. CONCLUSIONS: Postoperative adjuvant radiochemotherapy with up-to-date protocols can be recommended for routine treatment, if the surgeon or the patient desires to improve the usually remote prognosis after surgery alone. For those being indecisive or against adjuvant therapy, the participation in trials, e.g. the ESPAC 1 and 2 studies, is strongly recommended. Regarding our own positive experience with adjuvant regional chemotherapy and in view of the postresectional progression pattern, we currently favour adjuvant radiochemotherapy, with the chemotherapy delivered regionally via the celiac axis. This concept will be tested against surgery alone in the ESPAC 2 trial. Neoadjuvant therapies have a great potential, but should be conducted within studies, such as pre-, intra-, or postoperative radiotherapy.

Adenocarcinoma↗
PubMed1998

Adjuvant radiochemotherapy--what is the patients benefit?

BACKGROUND: Local relapse is a major problem after potentially curative rectal cancer surgery. Although the incidence of local recurrences may be reduced by specialized surgical techniques such as total mesorectal excision (TME), local relapse rates of 20% or higher are the surgical reality today. Studies using adjuvant postoperative radiotherapy, chemotherapy, radiochemotherapy or immunotherapy have tried to reduce local relapse rates and distant progression. Postoperative radiochemotherapy has been the recommended standard, after complete resection of Union Internationale Contra la Cancrum (UICC) stages II and III rectal cancers. In view of recent positive results with preoperative radiotherapy of TME without adjuvant therapy, we found it important to review the literature to update the recommendable adjuvant procedure in rectal cancer. METHOD/PATIENTS: The literature from 1985 to May 1998 was reviewed for studies trying to either confirm or improve adjuvant therapy in rectal cancer. Only randomized controlled trials were analyzed with regard to their effectiveness in reducing the absolute rates of local recurrence and improving survival. RESULTS: Two trials applying adjuvant radiotherapy were able to demonstrate the reduction of local relapse rates, one trial with marginal significance, both without impact on survival. Four trials involving 1104 patients with rectal cancer stages UICC II-III compared postoperative radiochemotherapy with either surgical controls, adjuvant radiotherapy or conventional radiochemotherapy. In these trials, local relapse rates were significantly reduced by 11-18%, and survival rates significantly improved by 10-14%. Severe acute toxicities occurred in 50-61% of the patients, compromising compatibility, and caused death in 0-1%. Small-bowel obstruction leading to surgery was noted in 2-6% and to death in up to 2% of the patients. Intraoperative radiotherapy (IORT) improved local control and survival after surgery of locally advanced disease/local relapse. CONCLUSION: In view of four trials demonstrating a significant benefit of postoperative radiochemotherapy and with regard to recent still-debatable results of preoperative short-term radiotherapy optimal surgery with lowest local relapse rates plus postoperative radiochemotherapy remains the actual recommendable standard for rectal cancer surgery in R0 resected tumors stages UICC II+III.

Chemotherapy, Adjuvant↗
PubMed1998

Multimodal therapy in rectal cancer.

The possibilities and results of multimodal treatment in rectal cancer were reviewed with respect to the results of surgical treatment only. Based on the results of 4 studies, reducing local relapse rates and increasing long-term survival rates significantly, postoperative radiochemotherapy (RCT) + chemotherapy (CT) should remain the recommended standard for R0 resected UICC II and III rectal cancers. Preoperative neoadjuvant radiotherapy (RT) reduced local relapse rates in 8 studies, and extended survival in one study that evaluated all eligible patients. Preoperative RT may evolve as standard, if the patient selection is improved and postoperative morbidity and long-term toxicity are reduced. Postoperative adjuvant RT reduced local relapses significantly in a single trial, and no impact on survival time is reported. Since postoperative RT is inferior to preoperative RT, this treatment cannot be recommended, if RT is chosen as a single treatment modality as an adjunct to surgery. Preoperative RCT + CT downstages resectable and nonresectable tumors and induces a higher sphincter preservation rate. This treatment may be routinely applied in nonresectable primary tumors or local relapses. Intraoperative RT could be added to this concept or be used together with preoperative/postoperative RT with the same indications. The results of local tumor excisions may be improved with pre- or postoperative RCT + CT.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1997

Oculomotor nerve and muscle abnormalities in congenital fibrosis of the extraocular muscles.

Congenital fibrosis of the extraocular muscles is an autosomal dominant congenital disorder characterized by bilateral ptosis, restrictive external ophthalmoplegia with the eyes partially or completely fixed in an infraducted (downward) and strabismic position, and markedly limited and aberrant residual eye movements. It has been generally thought that these clinical abnormalities result from myopathic fibrosis of the extraocular muscles. We describe the intracranial and orbital pathology of 1 and the muscle pathology of 2 other affected members of a family with chromosome 12-linked congenital fibrosis of the extraocular muscles. There is an absence of the superior division of the oculomotor nerve and its corresponding alpha motor neurons, and abnormalities of the levator palpebrae superioris and rectus superior (the muscles innervated by the superior division of the oculomotor nerve). In addition, increased numbers of internal nuclei and central mitochondrial clumping are found in other extraocular muscles, suggesting that the muscle pathology extends beyond the muscles innervated by the superior division of cranial nerve III. This report presents evidence that congenital fibrosis of the extraocular muscles results from an abnormality in the development of the extraocular muscle lower motor neuron system.

Abnormalities, Multiple↗
PubMed1997

The safety of asthma and allergy medications during pregnancy.

BACKGROUND: Although no asthma or allergy medications can be considered proven safe for use during pregnancy, these medications are often used to prevent the potential direct and indirect consequences of uncontrolled asthma or allergy. OBJECTIVE: The safety of asthma medications, antihistamines, and decongestants was assessed in a prospectively monitored cohort of 824 pregnant women with and 678 pregnant women without asthma. METHODS: Medications used since conception were recorded on each subject's initial visit (< 28 weeks' gestation). Thereafter, diary cards for medications were completed by the patient through the time of delivery. Perinatal outcomes were compared in exposed versus unexposed individuals. A multivariate analysis accounted for the potential effects of age, parity, smoking, race, weight gain during pregnancy, maternal pulmonary function, acute asthmatic episodes, and multiple medication exposure. RESULTS: No significant relationships were identified between major congenital malformations and first trimester or any exposure to beta-agonists, theophylline, cromolyn, corticosteroids, antihistamines, or decongestants. In the multivariate analyses, oral corticosteroids were independently associated with preeclampsia (odds ratio = 2.0, p = 0.027), but no other independent associations were observed between asthma or allergy medications and adverse perinatal outcomes. CONCLUSION: Use of most common asthma and allergy medications during pregnancy was not associated with increased perinatal risks. Maternal use of oral corticosteroids was independently associated with the occurrence of preeclampsia in this study, although the mechanism of this association is not clear. However, because prior observations suggest that severe asthma may be associated with maternal and/or fetal mortality, risk-benefit considerations still favor the use of oral corticosteroids when indicated for the treatment of asthma during pregnancy.

Administration, Inhalation↗
PubMed1997

Asthma treatment during pregnancy. What can be safely taken?

'Safe' pharmacological therapy for gestational asthma is defined as therapy during which the apparent risks of the drug appear to be lower than the maternal and potential fetal risks of uncontrolled asthma that could result if the drug were not used. Major malformations occur in 2 to 4% of all newborns, 1% of which can be attributed to medication in general. Information regarding the effects of drugs administered during pregnancy may come from animal studies, human case reports, and prospective cohort studies. Based on a review of the available information, it is recommended that mild asthma during pregnancy be managed with inhaled beta 2-agonists, as required; step therapy for moderate asthma would include inhaled sodium cromoglycate (cromolyn sodium), inhaled beclomethasone dipropionate and oral theophylline. Severe gestational asthma should be treated with oral corticosteroids at the lowest effective dosage. The pharmacological management of acute asthma during pregnancy should include nebulised beta 2-agonists and ipratropium bromide, and intravenous methylprednisolone. Intravenous aminophylline would not generally be recommended, unless the patient requires hospitalisation. Optimal medical practice medico-legal considerations demand that the patient's informed consent be obtained for that recommended gestational management programme.

Administration, Inhalation↗
PubMed1997

Asthma and allergy in pregnancy.

Rhinitis is extremely common during pregnancy, and asthma is one of the most common potentially serious medical problems to complicate pregnancy. Cutaneous allergy (urticaria/angioedema and eczema) also may occur during pregnancy. All of these entities may worsen with pregnancy in some patients and appear to improve in others. Uncontrolled asthma may directly threaten the fetus, and morbidity from the other illnesses may indirectly affect pregnancy through an effect on eating, sleeping, or emotional well-being. Appropriate diagnosis, avoiding triggering factors when possible; appropriate use of pharmacotherapy; and, when indicated, allergen immunotherapy usually allow these chronic conditions to be controlled during pregnancy so as to optimize both the health of the mother and that of her baby.

Asthma↗
PubMed1995

The 70S Escherichia coli ribosome at 23 A resolution: fitting the ribosomal RNA.

BACKGROUND: The ribosome--essential for protein synthesis in all organisms--has been an evasive target for structural studies. The best available structures for the 70S Escherichia coli ribosome or its 30S and 50S subunits are based on electron microscopical tilt experiments and are limited in resolution to 28-55 A. The angular reconstitution approach, which exploits the random orientations of particles within a vitreous ice matrix, can be used in conjunction with cryo-electron microscopy to yield a higher-resolution structure. RESULTS: Our 23 A resolution map of the 70S ribosome elucidates many structural details, such as an extensive system of channels within the 50S subunit and an intersubunit gap ideally shaped to accommodate two transfer RNA molecules. The resolution achieved is sufficient to allow the preliminary fitting of double-helical regions of an earlier three-dimensional ribosomal RNA model. CONCLUSIONS: Although we are still a long way from attaining an atomic-resolution structure of the ribosome, cryo-electron microscopy, in combination with angular reconstitution, is likely to yield three-dimensional maps with gradually increasing resolution. As exemplified by our current 23 A reconstruction, these maps will lead to progressive refinement of models of the ribosomal RNA.

Escherichia coli↗
PubMed1995

Perinatal outcomes in the pregnancies of asthmatic women: a prospective controlled analysis.

Prior studies have found an increased incidence of adverse perinatal outcomes of pregnancies in asthmatic mothers, but these studies have been poorly controlled for asthma therapy and other confounding factors. The purpose of this study was to assess perinatal outcomes in actively managed pregnant asthmatic women as compared with matched nonasthmatic controls. Using an inception cohort design, we studied a volunteer sample of 486 pregnant (< 28 wk) women with documented asthma and 486 pregnant nonasthmatic controls with normal pulmonary function. Cases and controls were matched for age, smoking status, parity, and year of delivery. Asthma was managed with step therapy to prevent acute asthmatic episodes and asthma symptoms that interfered with sleep or normal activity. Chronic hypertension was significantly more common (p = 0.007) in asthmatic subjects (3.7%) than in matched controls (1.0%). However, no significant differences in incidences of preeclampsia, perinatal mortality, preterm births, low-birth-weight infants, intrauterine growth retardation, or congenital malformations were observed in the pregnancies of the asthmatic women as compared with the matched controls. Trends were observed toward relationships between more severe asthma requiring emergency therapy or corticosteroids and increased incidences of preeclampsia and low-birth-weight infants, but these associations were not statistically significant. These data suggest that the overall perinatal prognosis for women with actively managed asthma during pregnancy is comparable to that for the nonasthmatic population.

Adult↗