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M Jakobsson

Publications and source records attributed to M Jakobsson.

At least 19 recordsLinked to original sources

The evolutionary history of the common chloroplast genome of Arabidopsis thaliana and A. suecica.

The evolutionary history of the common chloroplast (cp) genome of the allotetraploid Arabidopsis suecica and its maternal parent A. thaliana was investigated by sequencing 50 fragments of cpDNA, resulting in 98 polymorphic sites. The variation in the A. suecica sample was small, in contrast to that of the A. thaliana sample. The time to the most recent common ancestor (T(MRCA)) of the A. suecica cp genome alone was estimated to be about one 37th of the T(MRCA) of both the A. thaliana and A. suecica cp genomes. This corresponds to A. suecica having a MRCA between 10 000 and 50 000 years ago, suggesting that the entire species originated during, or before, this period of time, although the estimates are sensitive to assumptions made about population size and mutation rate. The data was also consistent with the hypothesis of A. suecica being of single origin. Isolation-by-distance and population structure in A. thaliana depended upon the geographical scale analysed; isolation-by-distance was found to be weak on the global scale but locally pronounced. Within the genealogical cp tree of A. thaliana, there were indications that the root of the A. suecica species is located among accessions of A. thaliana that come primarily from central Europe. Selective neutrality of the cp genome could not be rejected, despite the fact that it contains several completely linked protein-coding genes.

Arabidopsis↗

Enhanced ice sheet growth in Eurasia owing to adjacent ice-dammed lakes.

Large proglacial lakes cool regional summer climate because of their large heat capacity, and have been shown to modify precipitation through mesoscale atmospheric feedbacks, as in the case of Lake Agassiz. Several large ice-dammed lakes, with a combined area twice that of the Caspian Sea, were formed in northern Eurasia about 90,000 years ago, during the last glacial period when an ice sheet centred over the Barents and Kara seas blocked the large northbound Russian rivers. Here we present high-resolution simulations with an atmospheric general circulation model that explicitly simulates the surface mass balance of the ice sheet. We show that the main influence of the Eurasian proglacial lakes was a significant reduction of ice sheet melting at the southern margin of the Barents-Kara ice sheet through strong regional summer cooling over large parts of Russia. In our simulations, the summer melt reduction clearly outweighs lake-induced decreases in moisture and hence snowfall, such as has been reported earlier for Lake Agassiz. We conclude that the summer cooling mechanism from proglacial lakes accelerated ice sheet growth and delayed ice sheet decay in Eurasia and probably also in North America.

Journal Article↗

Chloroplast DNA indicates a single origin of the allotetraploid Arabidopsis suecica.

DNA sequencing was performed on up to 12 chloroplast DNA regions [giving a total of 4288 base pairs (bp) in length] from the allopolyploid Arabidopsis suecica (48 accessions) and its two parental species, A. thaliana (25 accessions) and A. arenosa (seven accessions). Arabidopsis suecica was identical to A. thaliana at all 93 sites where A. thaliana and A. arenosa differed, thus showing that A. thaliana is the maternal parent of A. suecica. Under the assumption that A. thaliana and A. arenosa separated 5 million years ago, we estimated a substitution rate of 2.9 x 10(-9) per site per year in noncoding single copy sequence. Within A. thaliana we found 12 substitution (single bp) and eight insertion/deletion (indel) polymorphisms, separating the 25 accessions into 15 haplotypes. Eight of the A. thaliana accessions from central Sweden formed one cluster, which was separated from a cluster consisting of central European and extreme southern Swedish accessions. This latter cluster also included the A. suecica accessions, which were all identical except for one 5 bp indel. We interpret this low level of variation as a strong indication that A. suecica effectively has a single origin, which we dated at 20 000 years ago or more.

Arabidopsis↗

Ice shelves in the Pleistocene Arctic Ocean inferred from glaciogenic deep-sea bedforms.

It has been proposed that during Pleistocene glaciations, an ice cap of 1 kilometre or greater thickness covered the Arctic Ocean. This notion contrasts with the prevailing view that the Arctic Ocean was covered only by perennial sea ice with scattered icebergs. Detailed mapping of the ocean floor is the best means to resolve this issue. Although sea-floor imagery has been used to reconstruct the glacial history of the Antarctic shelf, little data have been collected in the Arctic Ocean because of operational constraints. The use of a geophysical mapping system during the submarine SCICEX expedition in 1999 provided the opportunity to perform such an investigation over a large portion of the Arctic Ocean. Here we analyse backscatter images and sub-bottom profiler records obtained during this expedition from depths as great as 1 kilometre. These records show multiple bedforms indicative of glacial scouring and moulding of sea floor, combined with large-scale erosion of submarine ridge crests. These distinct glaciogenic features demonstrate that immense, Antarctic-type ice shelves up to 1 kilometre thick and hundreds of kilometres long existed in the Arctic Ocean during Pleistocene glaciations.

Journal Article↗

[Midazolam (Dormicum) in terminal anxiety and agitation. The last choice alternative in palliative care].

Although midazolam has been proposed for the treatment of a variety of conditions such as anxiety, dyspnoea, hiccups and status epilepticus, terminal agitation is the only condition where its use is based on a reasonably large number of published clinical studies. A causal approach is generally recommended. Whenever possible, the aetiological condition (pain, fever, constipation, etc.) should be corrected. Such general measures as ensuring a peaceful, familiar environment, and the use of a night light, fluid therapy to counteract dehydration, and antipyretics for fever are beneficial. When symptomatic treatment is needed, drugs with little anticholinergic effect are to be recommended. The use of benzodiazepines as single drug treatment may exacerbate the condition. Haloperidol or risperidone (which has fewer side effects) are recommended. If the agitation is marked, a common strategy is to add lorazepam. Chlormethiazole is an alternative. Subcutaneous midazolam should be reserved for refractory cases. Attention should be paid to dosage, reduced doses being given to the elderly, patients on opioid medication, and patients with impaired liver or renal function. Overdosage may induce deep sedation, and result in carbon dioxide retention and subsequently heart failure and pulmonary oedema which may be fatal.

Anti-Anxiety Agents↗

A randomised placebo controlled study with ondansetron in patients undergoing fractionated radiotherapy.

BACKGROUND: There are few randomised studies comparing anti-emetic drugs for the prevention of nausea and vomiting in patients treated with fractionated radiotherapy. The aim of the study was to compare the anti-emetic efficacy of 8 mg dose ondansetron twice a day with placebo. MATERIALS AND METHODS: One hundred eleven patients who were to commence a course of 10 or more daily fractionated radiotherapy including the abdomen were included in the study. The patients recorded daily emesis, nausea and bowel habit and graded weekly symptoms of nausea, vomiting, diarrhoea and lack of appetite. The EORTC C30 questionnaire was completed. RESULTS: 67% of patients given ondansetron had complete control of emesis compared with 45% of patients with placebo (P < 0.05). The number of emetic episodes recorded on the worst day was 1.4 for the ondansetron group and 3.1 for the placebo group (P < 0.01). Patients given ondansetron had fewer days with emesis and nausea compared with placebo (P < 0.05). The mean sum score of patients weekly grading of symptoms showed that the ondansetron group had less inconvenience than the placebo group (P < 0.05). This difference persisted during the first three weeks, but not thereafter. Similarly, some quality of life measures showed significant differences in favour of the ondansetron group. More patients (n = 13) withdrew due to lack of efficacy in the placebo group compared with patients (n = 8) in the ondansetron group. CONCLUSIONS: The present study illustrates that prophylactic anti-emetic administration of ondansetron is effective in preventing nausea and vomiting in patients undergoing fractionated radiotherapy of the abdomen.

Abdomen↗

Treatment of Hodgkin's disease: the Swedish National Care Programme experience.

Since 1985 a Swedish National Care Programme has provided tailored principles for the diagnosis, staging, treatment and follow-up of patients with Hodgkin's disease (HD). This report gives the rationale behind the recommendations and presents treatment results for 648 patients diagnosed between 1985 and 1989 after a median follow-up of 70 months. Two hundred and twenty-nine (35%) patients were over 60 years of age. Treatment results for patients below 60 years of age in early and intermediate stages were favourable, provided the recommendations were followed. In advanced stages, the outcome was inferior in patients with CS IIB bulky disease and stage IVB. The prognosis of elderly patients remains poor, although it is too early to evaluate any impact of revisions made in 1989. The tailored principles, which usually entail less staging and/or treatment than is generally the case in the early and intermediate stages, produced favourable results when applied to an unselected group of patients with HD. Only minor changes were made in the recommendations during the 1994 revision.

Adolescent↗

Treatment of early and intermediate stages of supradiaphragmatic Hodgkin's disease: the Swedish National Care Programme experience. Swedish Lymphoma Study Group.

PURPOSE: Since 1985 a Swedish National Care Programme has provided tailored principles for the staging, treatment and follow-up of patients with Hodgkin's disease (HD). This report presents treatment results for all patients below 60 years of age who were diagnosed with early and intermediate stages, between 1985 and 1989. PATIENTS AND TREATMENT: During that period, 210 patients with supradiaphragmatic HD in clinical (CS) and pathological (PS) stages IA+IIA, PS IB+IIB, and PS III1 A were diagnosed in five Health Care Regions in Sweden. In patients with CS IA, staging laparotomy was not recommended provided that the radiological assessment of the abdomen was adequate, whereas this procedure was recommended in stages CS IB, IIA and IIB in order to minimize treatment. In the absence of bulky mediastinal disease, patients with CS+PS IA and PS IIA were treated with mantle (occasionally mini-mantle) irradiation alone, while patients with bulky disease, as well as those with stages PS IB+IIB+III1 A, were treated with one cycle of MOPP/ABVD prior to mantle (PS III1 A sub-total nodal) irradiation. Full chemotherapy followed by radiotherapy to initial sites with bulky disease was recommended for patients with CS IIA who did not undergo laparotomy. RESULTS: After a median follow-up in excess of five years, treatment results are 'favourable' for all stages, provided the recommendations were followed. In patients with CS+PS IA treated according to the recommendations, recurrence rates were 14% (9/65) with all but one patient (64/65, 98%) remaining in continuous first or second remission. These figures were worse in patients treated inadequately (9/26 [35%] and 22/26 [85%], respectively). In PS IIA, adequately-treated patients had a recurrence rate of 13% (7/52) whereas 5/7 (71%) of those with bulky disease who received only mantle irradiation developed recurrences. Similar patterns also emerged in patients with CS IIA, PS IB+IIB and PS III1 A. CONCLUSIONS: The tailored principles, which usually entail less staging and/or treatment than is generally the case, produced favourable results when applied to an entirely unselected group of patients with early and intermediate stages of HD.

Adolescent↗

Carboplatin and etoposide in extensive small cell lung cancer.

The combination of carboplatin and etoposide was evaluated in 61 previously untreated patients with extensive small cell lung cancer. Treatment was given at four-week intervals with 450 mg/m2 of carboplatin intravenously (i.v.) on day 1 and etoposide 100 mg/m2 i.v. on days 1-3. The response was complete in 5 (9%) and partial in 28 (50%) of the 56 evaluable patients (overall response rate 59%). The median time to progression after response as well as the median survival time in all evaluable patients was 4.6 months. WHO grade 3 and 4 leukopenia and thrombocytopenia occurred in 8% and 11% of the courses respectively. Two treatment-related deaths were registered. The combination of carboplatin and etoposide used in the present study produced acceptable response rate and toxicity, but duration of response and median survival were shorter than expected from earlier studies.

Adult↗

Samarium-153-EDTMP in bone metastases.

Thirty-five patients with painful bone metastases arising from a variety of tumor types underwent a clinical trial in which 153Sm-EDTMP was injected as a single intravenous dose. The injection ranged in amount from 330 MBq to 1110 MBq of 153Sm-EDTMP. Pain relief usually occurred within one week after administration. The duration of pain relief lasted from 2 to 17 weeks. A detectable degree of pain palliation was experienced by 80% of the treated patients; 54% reported substantial or complete pain relief. Due to the small number of patients, no clear-cut dose-related response was detectable. Moderate myelosuppression was observed in one patient (WHO grade III). The metastatic lesion-to-normal bone ratios remained constant (varying from 1.5 to 4.8) for at least 5 days post-injection. 153Sm cleared very rapidly from the blood. Less than 1% of the injected dose remained in circulation at 4 hours post-injection. No local accumulation of the tracer could be detected outside the skeleton. Urinary excretion was quite complete at 6 hours post-injection. The biodistributions of 153Sm-EDTMP and 99mTc-DPD are very similar in metastatic and normal bone; thus, bone scanning can be used for patient selection and followup. According to our results, it seems that higher doses of 153Sm-EDTMP can be given safely and without any irreversible myelosuppression.

Bone Neoplasms↗

A phase II study of metastatic melanoma treated with a combination of interferon alfa 2b, dacarbazine and nimustine.

52 patients with metastatic melanoma have been treated with a combination of recombinant interferon-alfa-2b, dacarbazine and nimustine. The objective response rate was 23% with 9 complete responses (CR) and 3 partial responses (PR). The mean duration of the response was 18+ months for CR (6-31+ months) and 7 months for PR patients (4-10 months). The mean survivals were 24+ months (8-38 months) and 7 months (4-12 months), respectively. The mean duration of the response for patients with stable disease was 10+ months (2-48+ months) and the mean survival 17+ months (3-48+ months), while the patients with progressive disease died within 12 months (mean 4 months). The best responding sites were the lymph node, the lung and the subcutaneous metastases. Myelosuppression was the main adverse effect of the therapy. WHO grade 3-4 toxicity was seen in 27 patients leading to delay and reduced dosage of therapy; in 4 patients treatment was discontinued, 8 patients had no side effects. Combination therapy with interferon and dacarbazine and nimustine for metastatic melanoma offers no advantage over interferon and dacarbazine.

Adult↗

Vincristine, doxorubicin and cyclophosphamide with and without etoposide in limited small cell lung cancer.

A total of 80 patients with limited disease of small cell lung cancer were randomized to receive either vincristine 1 mg/m2 (max. 2 mg), doxorubicin 50 mg/m2 and cyclophosphamide 750 mg/m2 (VAC) i.v. on day 1, or the same drugs and etoposide 80 mg/m2 i.v. daily for 3 days (VACE) every 3 weeks for nine courses. Chest irradiation was given in both regimens after the second course. The response rate was 84% for VAC (41% complete responses) and 75% for VACE (46% complete responses). The median survival time was 10 months with VAC regimen, and 14 months with VACE (difference statistically not significant). The median duration of remission was 8 months with VAC and 14 months with VACE (p = 0.03), and the median survival for complete or partial responders was 12 months and 20 months respectively (p = 0.006). Myelosuppression was significantly greater in the VACE group, and there was one treatment related death in the group receiving VACE. In this study the addition of etoposide to VAC improved the duration of response, but did not lead to longer survival of patients with limited disease of small cell lung cancer.

Adult↗

Inoperable non-small cell lung cancer: radiation with or without chemotherapy.

We report a randomized multicentre study of split-course radiotherapy (RT), with or without combination chemotherapy (CT), in 238 patients with inoperable non-small cell lung cancer (NSCLC), previously untreated, confined to one hemithorax and the mediastinal nodes. In both treatment groups RT consisted of 55 Gy in 20 F given over 7 weeks with a 3-week rest interval. CT consisted of the 3-drug regimen CAP: C = cyclophosphamide 400 mg/m2, A = adriamycin 40 mg/m2, P = cisplatin 40 mg/m2; 2 cycles of CAP given before RT, one during the rest interval and six after RT. Seventy per cent in the RT arm and 67% in the RT-CT arm had epidermoid carcinoma. No significant difference was apparent between the RT and the RT-CT arms with respect to objective response rates (CR + PR) (44 and 49%, respectively), median duration of response (278 and 320 days), local failure (31 and 20%), distant progression (23 and 20%) or median survival (311 and 322 days). The survival figures showed an almost significant (P = 0.05) therapeutic advantage of the combined regimen with stage IIIM0 disease. Progressive disease was the cause of death in 92% and 88%. We conclude that chemotherapy did not contribute significantly to either local control or survival as compared to radiotherapy alone.

Antineoplastic Combined Chemotherapy Protocols↗