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Biomedical subjects

J Sorge

Publications and source records attributed to J Sorge.

At least 19 recordsLinked to original sources
PubMed2000

The lesson from cancer pain.

The success of the WHO guidelines for the treatment of cancer pain indicates that cancer pain was previously undertreated. At the heart of these guidelines lies the three-step analgesic ladder, the last two steps of which consist of prescribing opioids. Today, the use of opioids in cancer patients is generally accepted, but there are still some concerns over the risks of addiction and adverse reactions, and opioids are sometimes withheld from patients who would otherwise benefit from them. However, it has been shown that such concerns are misplaced: the risks of severe adverse reactions and addiction are low when opioids are used correctly in patients with chronic pain. The use of opioids to treat benign pain is even less widely accepted in many countries, despite recommendations that they should be prescribed. It is emphasized that the use of opioids is a valid option for treating benign pain, and they should not be withheld from patients who need them. Opioids are always indicated when other therapeutic options, including NSAIDs, have failed or are contraindicated. When opioids are prescribed, procedures should be followed to provide the patient with maximum benefit and minimum risk.

Drug Prescriptions↗
PubMed1997

[Strong opioids for treatment of chronic pain: a meta-analysis].

In the following presentation 59 German and English articles on the use of strong opioids in chronic pain syndromes are analysed. Studies concerning the epidural, intrathecal, intracerebroventricular and transdermal application of opioids were excluded. The articles were attributed to different study levels according to their contents. The majority of articles (n=39, 66.1%) consisted of case presentations, while only 33.9% of the articles presented randomised (n=15) or non-randomised (n=5) study designs. The analgesic effect of the strong opioids morphine, buprenorphine and methadone in oral, rectal, subcutaneous and intravenous forms of application was confirmed for cancer-associated and non-cancer-associated chronic pain. Altogether there is a lack of controlled clinical studies.

English Abstract↗
PubMed1996

[Supply of opioid analgesics to outpatients with cancer pain].

INTRODUCTION: Treatment of chronic cancer pain with strong opioids is indicated in about 60-70 % of patients. Surprisingly, these very potent analgesics are prescribed with great reservations in many countries, including Germany. The aim of our investigation was to analyse the supply of opioid analgesics to outpatients with cancer pain in the region of Hannover, which has about 1.1 million inhabitants. METHODS: In Germany special prescription forms, i. e. triplicate forms, have to be used for the prescription of strong opioids. At the time when our investigation took place prescriptions for outpatients had to be renewed every 7 days. For two observation periods of 6 months lasting from January to June 1988 and from January to June 1991 all of the opioid prescription forms that had been issued by general practitioners for clients of the AOK Hannover (one of the major medical insurance companies) were evaluated. The reasons for prescribing opioids were analysed by recording the diagnosis. The individual treatment period on an outpatient basis during these 6 months was determined, excluding, e. g. days of hospitalization. RESULTS: During the two observation periods only 16.2 % (1988) and 19.5 % (1991) of the practitioners in the region of Hannover prescribed strong opioids to outpatients. The majority of the practitioners consisted of general practitioners and specialists in internal medicine. Although these two groups mainly function as family doctors who are responsible for the basic therapeutical needs of their patients, only 22.6-33.8 % of these doctors prescribed opioids to outpatients. In two-thirds of the patients, cancer pain was the reason for prescribing the drug. The total number of patients with a prescription for cancer pain was 164 in 1988 and 196 in 1991. Altogether 1002 prescription forms in 1988 and 1065 prescription forms in 1991 had been issued for these patients. Applied to the individual treatment period as an outpatient, only 36.0 % of the patients in 1988 and 32.1 % in 1991 received a regular prescription of strong opioids every 7 days. The mean time interval between separate prescriptions was 16.8 +/- 25.4 days in 1988 and 19.4 +/- 29.1 days in 1991. Accordingly, the majority of patients with chronic cancer pain had been supplied with opioids only occasionally. CONCLUSION: Our data indicate a significant undertreatment of outpatients suffering from cancer pain. Taking into account the estimated total number of patients suffering from cancer, only 14.5 % (1988) and 19.0 % (1991) of all outpatients in need of strong opioids were supplied sufficiently with those analgesics. Comparing the results from the observation period in 1988 with the results from 1991 it becomes obvious that the situation has not changed. There are different reasons for the insufficiency of opioid treatment: many physicians as well as their patients are still afraid of the side effects of strong opioids. Therefore, it is necessary to improve education concerning this issue. The legal restrictions on the use of narcotics and their complexity are another important reason for doctors not to prescribe strong opioids. In 1993 the regulations were simplified; nevertheless, this has not led to a profound change in the attitude of the prescribing practitioners. Thus, further changes in legislation seem to be necessary so that the requirements for the prescription of strong opioids do not differ from other drugs.

English Abstract↗
PubMed1996

[Not Available].

Explore the source record for details and available documents.

Journal Article↗
PubMed1992

[Continuous ambulatory intravenous morphine infusion for pain therapy in advanced ovarian cancer].

We report on a female outpatient with cancer of the ovary, who received continuous intravenous morphine infusion for terminal pain control. The patient was treated over a period of 48 days with a morphine dosage ranging from 10 to 60 mg/h, which kept her free of pain. With treatment, she was alert, communicative with her relatives and moved freely. At a later stage, we complemented the treatment with Diazepam and Haloperidol. No side-effects were observed over the whole period of morphine infusion.

Diazepam↗
PubMed1991

Identification of the second common Jewish Gaucher disease mutation makes possible population-based screening for the heterozygous state.

Gaucher disease is an autosomal recessive glycolipid storage disease characterized by a deficiency of glucocerebrosidase. The disease is most common in persons of Ashkenazi Jewish ancestry and the most common mutation, accounting for about 75% of the mutant alleles in this population, is known to be an A----G substitution at cDNA nucleotide (nt) 1226. Screening for this disease has not been possible because nearly 25% of the mutant alleles had not been identified, but linkage analysis led to the suggestion that most of these could be accounted for by a single mutation. We now report the discovery of this mutation. The insertion of a single nucleotide, a second guanine at cDNA nt 84 (the 84GG mutation), has been detected in the 5' coding region of the glucocerebrosidase gene. The amount of mRNA produced is shown to be normal but since the frameshift produced early termination, no translation product is seen. This finding is consistent with the virtual absence of antigen found in patients carrying this mutation. The 84GG mutation accounts for most of the previously unidentified Gaucher disease mutations in Jewish patients. The common Jewish mutation at nt 1226, the 84GG mutation, and the less-common mutation at nt 1448 accounted for 95% of all of the Gaucher disease-producing alleles in 71 Jewish patients. This now makes it possible to screen for heterozygotes on a DNA level with a relatively low risk of missing couples at risk for producing infants with Gaucher disease.

Age Factors↗
PubMed1990

[Long-term therapy of tumor pain using morphine-retard tablets].

We analysed the effect of sustained-release morphine tablets in 174 patients with severe cancer pain. A good relief of pain could be obtained in 65% of the patients within the first week and in 80% of the patients at the end of therapy. The mean daily dose was at 178 mg morphine, six patients needed more than 1000 mg per day. The sustained-release morphine was given at fixed intervals, in 80% of the cases every eight hours. No severe side-effects were associated with long-term morphine therapy. We often saw nausea and vomiting, constipation and drowsiness, but these side-effects decreased after the first weeks of treatment. Only in ten patients we had to stop therapy because of side-effects. Morphine can be used successfully in the treatment of cancer pain for long periods without concern about tolerance.

Administration, Oral↗
PubMed1990

[Pain therapy in gynecologic neoplasms].

A great number of patients with gynaecological malignant diseases suffer from severe pain, caused, for example, by bone metastases of breast cancer or tumour infiltration of the pelvis and the lumbar plexus in uterine cancer. Several methods of treatment are available depending upon the origin of pain. It is possible to achieve pain relief by radiotherapy or by cytostatic therapy. Sometimes, anaesthesiological and neurosurgical measures are successful, but the most important method is treatment with analgesics. Strong opioids are given, if pain relief is insufficient under treatment with non-narcotic drugs or weak opioids, like codeine. Morphine and other strong opioids are not reserved for pain control only in terminally sick women, as they can be administered successfully for long periods without severe side effects. If possible, the oral route should be selected. If vomiting occurs, or if patients are unable to take oral medication, morphine can be given peridurally, intrathecally or by infusion. Often, an additional treatment is necessary with different medicaments like tricyclic antidepressants and corticosteroids.

Analgesics↗
PubMed1990

A glucocerebrosidase fusion gene in Gaucher disease. Implications for the molecular anatomy, pathogenesis, and diagnosis of this disorder.

The molecular diagnosis of Gaucher disease has been difficult due to the existence of several different point mutations in the glucocerebrosidase gene and due to the presence of a tightly linked, highly homologous pseudogene. We now report the occurrence of a "Lepore-like" glucocerebrosidase fusion gene in which the 5' end is the functional gene and the 3' end is the pseudogene. This further complicates the molecular diagnosis of Gaucher disease but sheds light on the molecular anatomy of the glucocerebrosidase gene complex and on the pathogenesis of this important storage disease.

Adult↗
PubMed1990

High level transcription of the glucocerebrosidase pseudogene in normal subjects and patients with Gaucher disease.

Gaucher disease is due to mutations involving the glucocerebrosidase gene. A closely homologous pseudogene is located approximately 16 kD downstream from the functional gene. Sequence analysis of clones from cDNA libraries made from skin fibroblast cultures showed several independent clones with the sequence of an aberrantly processed pseudogene message. Examination of cellular RNA from lymphoblasts or fibroblasts obtained from thirteen Gaucher disease patients, one Gaucher disease heterozygote, and four normal subjects showed that the pseudogene was consistently transcribed, and that in some cases the level of transcription seemed to be approximately equal to that of the functional gene. The transcription of the pseudogene must be taken into account when attempting to detect mutations of glucocerebrosidase by the study of cDNA libraries.

Base Sequence↗
PubMed1989

Prediction of severity of Gaucher's disease by identification of mutations at DNA level.

The polymerase chain reaction was used to detect four mutations in the DNA of 47 unrelated patients with type I Gaucher's disease (94 Gaucher's disease alleles). Two of the mutations, 1226 and 1448, and a new mutation (XOVR) representing cross-over between the glucocerebrosidase gene and its closely linked pseudogene, were found. There were five genotypes--namely, 1226/1226, 1226/1448, 1226/XOVR, 1226/?, and ?/? (where "?" indicates that none of the four known mutations was present). Severity of the disease was assessed with a scoring index according to age at diagnosis and extent of organ involvement. Mutation 1226 was associated with a mild clinical phenotype, and mutation 1448 with a more severe phenotype. Mutation 1226 is the most common cause of Gaucher's disease in Jewish patients.

Adolescent↗
PubMed1989

Mouse retroviral sequences acquired by cell lines after passaging through nude mice detected by hybridization of the fms probe pSM3.

The expression of a large RNA transcript, 8.5 to 9.5 kilobases, possibly related to the fms oncogene in mouse, rat, and human tumor cells, has been described in the literature. However, the pSM3 fms probe used to detect this gene transcript contains a significant amount of the pol gene of the Susan McDonough strain of feline sarcoma virus from which it was derived. Using a fms probe which does not contain any viral pol sequences, no such "fms-related" transcripts were detected in cell lines previously reported to express the large transcripts. These cell lines did express a large 9.5-kilobase transcript which hybridized to a probe for murine leukemia virus. Partial sequence analysis of the 9.5-kilobase transcript detected with the pSM3 probe in transformed rat cells indicated sequence homology with AKV murine leukemia virus. Thus, the presence of large RNA transcripts, interpreted by us and others as being related to the oncogene fms, appears to be due to the expression of mouse retroviral sequences which hybridize to the viral pol region contained in the pSM3 fms probe. In the case of rat and human cells, such sequences appear to be acquired after the cells have been passaged in nude mice. These results should serve as a reminder of the important biohazard and data interpretation implications for investigations in which cells transfected with retroviral vector constructs are injected into nude mice, because rescue of the recombinant sequences in these cells could occur following infection by endogenous murine retroviral particles.

Animals↗
PubMed1989

Retroviral-mediated transfer and expression of hepatitis B e antigen in human primary skin fibroblasts and Epstein-Barr virus-transformed B lymphocytes.

Previously, an amphotropic retroviral expression system coding for the neomycin resistance gene was developed and used to synthesize hepatitis B e antigen (HBeAg) and hepatitis B core/e antigen (HBc/eAg) in transfected mouse NIH 3T3 fibroblasts (A. McLachlan et al., 1987, J. Virol. 61, 683-692). In the present study, these transfected cell lines were infected with a helper amphotropic murine leukemia virus resulting in the production of infectious recombinant retrovirus. The recombinant retrovirus was examined for its capacity to transmit resistance to the antibiotic, G418, and to express hepatitis B virus antigens in mouse NIH 3T3 fibroblasts, human primary skin fibroblasts, and Epstein-Barr virus (EBV)-transformed B lymphocytes. A mouse NIH 3T3 fibroblast clone was generated which produced recombinant retrovirus with the capacity to transmit HBeAg expression to these murine and human cell lines. In contrast, it was not possible to transmit HBc/eAg synthesis efficiently to these cell lines by recombinant retroviral infection. The difference between the efficiencies of transmission of HBeAg and HBc/eAg expression by recombinant retroviral-mediated infection was not predicted as the expression vector coding for HBc/eAg synthesis differs only by the deletion of approximately 90 nucleotides of HBV DNA sequence from the vector coding for HBeAg synthesis.

Adult↗
PubMed1987

Molecular cloning and chemical synthesis of a region of platelet glycoprotein IIb involved in adhesive function.

Membrane glycoprotein (GP) IIb-IIIa is a component of a platelet adhesive protein receptor. A region of the heavy chain of GPIIb, defined by the monoclonal antibody PMI-1, is involved in adhesion receptor function. We have localized and chemically synthesized this region of GPIIb. A cDNA clone that directs the synthesis of a fusion protein reactive with the PMI-1 antibody was isolated from a phage lambda gt11 expression library constructed with mRNA from an erythroleukemia (HEL) cell line. The deduced amino acid sequence of this clone indicates that it spans the light-heavy chain junction of GPIIb and contains a portion of the carboxyl terminus of the heavy chain and the amino terminus of the light chain. The PMI-1 epitope was found to be contained within a 9-kDa staphylococcal V8 protease fragment of GPIIb, and such a fragment was predicted within the putative heavy-chain sequence. A computerized antigen prediction program identified a single sequence with a high probability of containing a continuous epitope. A synthetic 17-residue peptide containing this sequence binds PMI-1 and inhibits PMI-1 binding to GPIIb-IIIa. The peptide-antibody complex has an approximate Kd of 1.2 microM, which compares to a Kd of 0.95 microM for PMI-1 binding to GPIIb. The region containing the PMI-1 epitope shows no similarity to corresponding regions of two other adhesion receptors, indicating that this portion of GPIIb may function in activities unique to the platelet receptor.

Amino Acid Sequence↗
PubMed1987

Complete correction of the enzymatic defect of type I Gaucher disease fibroblasts by retroviral-mediated gene transfer.

Glucocerebrosidase cDNA and the neomycin-resistance gene (neo) were cloned into a retrovirus vector. Mouse fibroblasts infected with this vector expressed human glucocerebrosidase, which was readily distinguished from the mouse enzyme using mouse monoclonal anti-glucocerebrosidase antibodies. Cultured fibroblasts and transformed lymphoblasts from patients with type I Gaucher disease were infected with the retrovirus rescued from the mouse fibroblasts by a helper virus. Transformed cells were selected with the antibiotic G418. The enzyme activity of cells infected with virus containing glucocerebrosidase cDNA was restored to normal, while uninfected cells or cells infected with virus containing only the neo gene did not produce glucocerebrosidase.

Animals↗
PubMed1987

Expression of hepatitis B virus surface and core antigens: influences of pre-S and precore sequences.

Amphotropic retroviral expression systems were used to synthesize hepatitis B virus surface antigen (HBsAg) and core antigen. The vectors permitted establishment of cell lines which expressed antigen from either the retroviral long terminal repeat or the mouse metallothionein-I promoter. HBsAgs were synthesized containing no pre-S sequences, pre-S(2) sequences alone, or pre-S(1) plus pre-S(2) sequences. Inclusion of pre-S(2) sequences did not affect the secretion or density of HBsAg particles but did reduce their mass by approximately 30%. Addition of pre-S(1) sequences almost completely abolished secretion of HBsAg and resulted in its localization in an aqueous-nonextractable pre- or early-Golgi cellular compartment. HBsAg was localized to the cytoplasm of the cell. This localization was unaffected by the presence of pre-S sequences in the antigen. Cell lines synthesizing hepatitis B antigens from core DNA fragments, containing or not containing precore sequences, secreted hepatitis B e antigen. However, the absence of precore DNA sequences resulted in additional synthesis of hepatitis core antigen, which was predominantly nuclear in localization.

Animals↗