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Biomedical subjects

L Holmberg

Publications and source records attributed to L Holmberg.

At least 55 records · Page 3Linked to original sources

Solid human embryonic spinal cord xenografts in acute and chronic spinal cord cavities: a morphological and functional study.

While therapeutic spinal cord grafting procedures are of interest in the chronic spinal cord injury stage, previous experimental grafting studies, including human spinal cord tissue, have mainly focused on the acute stage. Therefore, solid human embryonic spinal cord grafts were implanted in acute or chronic spinal cord aspiration cavities of immunodeficient rats to compare the morphological and locomotor outcome to that of lesion alone cases. Locomotor function was assessed using the Basso, Beattie, and Bresnahan open-field locomotor rating scale up to 6 months, while the morphological evaluation of graft survival, growth, and integration was performed at 6 weeks or 6 months after implantation. Graft survival was 94% in both lesion models, while graft growth was enhanced in the chronic compared to the acute cavity group. Human specific Thy-1 and neurofilament immunoreactive fibers were observed up to 7 mm into host white matter, while aminergic fibers were observed up to 1 mm into the grafts. Abundant calcitonin gene-related peptide immunoreactive fibers in the grafts in the absence both of immunoreactive cell bodies and colocalized human-specific neurofilament immunoreactivity, suggested host fiber ingrowth. At 6 months, the grafted cases presented less central canal deformation and lower glial fibrillary acidic protein immunoreactivity at the host cavity border compared to that of the nongrafted cases. The strong compensatory regain of locomotor function after unilateral spinal cord lesions was not affected by the human spinal cord grafts. In conclusion, solid human embryonic spinal cord tissue transplanted to a cavity in the adult injured spinal cord results in beneficial morphological effects in both the acute and chronic spinal cord lesion.

Animals↗

Time trends in the results of breast conservation in 4694 women.

In a population-based cohort of 4694 women with invasive breast cancer, operated upon with breast conserving surgery (BCS) in 1981--1990 and followed through to 1997, we studied how this technique had been adopted into clinical practice, especially with reference to the use of radiotherapy (RT). Our main aim was to see whether there was a drift in the risk of local recurrence and breast cancer death over time. During the 30,151 person-years of observation in the cohort, there were 582 local recurrences, 456 breast cancer deaths and 438 deaths due to other causes. Postoperative RT was given to 70.2%, but usage increased over the period. The women not receiving RT were mostly elderly, but also in women <70 years, 20.4% did not receive RT. The risk for local recurrence after RT were 7.6 and 17.8% at 5 and 10 years, respectively. Without RT, more than 30% had a local recurrence at 10 years. Thus, the choice not to irradiate failed to target women at a low risk. In a multivariate Cox analysis taking tumour size, nodal status, age at operation and RT into account, there was a trend for a higher risk of local recurrence in the later time period, relative hazard 1.5 (95% confidence interval (CI) 1.0--2.1). Corrected survival was 93.3 and 85.2% at 5 and 10 years, respectively.

Adult↗

Reduced utilisation of specialist care among elderly cancer patients: a randomised study of a primary healthcare intervention.

The aim of this study was to evaluate the effect of an individual support (IS) intervention including intensified primary healthcare on the utilisation of specialist care among cancer patients, and to investigate if such an effect was modified by the patient's age (less than 70 years or 70 years and more). Newly diagnosed cancer patients (n=416) were randomised between the intervention and a control condition, and data were collected on the utilisation of specialist care within 3 months from inclusion. Intensified primary healthcare comprised extended information from the specialist clinics, and education and supervision in cancer care for general practitioners (GPs) and home-care nurses. The support given also included interventions designed to diminish problems of weight loss and psychological distress. The intervention reduced the number of admissions (NoA) and the days of hospitalisation (DoH) after adjustment for weight loss and psychological distress, but only for older patients. Older patients randomised to the intervention (n=82) experienced 393 fewer DoH than the older control patients (n=79). In addition, the proportion of older patients in the IS group who utilised acute specialist care was smaller compared with older control patients group. The conclusion is that older cancer patients' utilisation of specialist care may be reduced by intensified primary healthcare services.

Age Factors↗

Trafficking of CD34+ cells into the peripheral circulation during collection of peripheral blood stem cells by apheresis.

The number of CD34+ cells collected during apheresis is related to the volume of blood processed. In large-volume apheresis (LVL) procedure, more cells can be collected than were originally present in the peripheral blood at the start of the collection procedure. We prospectively studied the levels of CD34+ cells in the blood and apheresis product during LVL procedures for 21 patients with acute myelogenous leukemia or multiple myeloma. These patients experienced a slow decline in blood CD34+ cell concentrations during the apheresis procedure. No patient demonstrated a sustained rise in CD34+ cell counts as a result of the procedure. The number of CD34+ cells collected exceeded the number calculated to be in the peripheral blood at the start of the procedure by an average of 3.0-fold. The efficiency of collection for CD34+ cells averaged 92.6% and did not vary with speed of blood processing, diagnosis, or mobilization regimen. The calculated release of CD34+ cells from other reservoirs into the peripheral blood averaged 3.71 x 10(6)/min (range, 0.36-13.7 x 10(6)/min), and correlated (r = 0.82) with the concentration of these cells in the peripheral blood at the start of the procedure. These data show that the apheresis procedure used in this study does not affect the release of CD34+ cells in a cytokine-treated patient. LVL will result in collection of larger quantities of CD34+ cells than procedures involving processing of smaller volumes of blood, but the number of cells collected is limited by the rate of release of these cells into the peripheral circulation where they are accessible for collection.

Acute Disease↗

Incidence and geographical distribution of sudden infant death syndrome in relation to content of nitrate in drinking water and groundwater levels.

BACKGROUND: Previous studies indicate that the enteral bacterial urease is inhibited in victims of sudden infant death syndrome (SIDS). One possible inhibitor of this bacterial activity is nitrate. If ambient pollution by nitrate is involved in the etiology of SIDS only a fraction of the nitrate concentration not infrequently found in drinking water would be enough for this inhibition. METHODS: Occurrence of SIDS (n = 636) in Sweden during the period 1990 through 1996 were analysed regarding geographical and seasonal distribution in relation to the nitrate concentration in drinking water and changes in the groundwater level. RESULTS: Both the birth rate and the incidence of SIDS decreased during the study period. One quarter of the municipalities constituting 11% of the population had no cases, the maximum incidence being 6.5 per 1000 live births. Seasonality: The northernmost parts of the country had its highest incidence when the rest of the country had its lowest incidence, and the occurrence of individual deaths was associated with the recharge of groundwater which increases its nitrate content. The local incidence of SIDS was correlated (rs = 0.34-0.87) to maximally recorded concentrations of nitrate in drinking water. CONCLUSIONS: The seasonal distribution of SIDS was widely different from the south to the north of the country and seems to be associated with differences in the groundwater level changes subsequent to precipitation, frost penetration, and melting of snow. Use of drinking water with high peak concentrations or great variations in nitrate concentration was correlated to the incidence of SIDS.

Humans↗

Pre-operative oestradiol levels - relation to survival in breast cancer.

AIMS: There are clinical observations that operation during the luteal phase of the menstrual cycle (with high oestradiol levels) may positively influence prognosis in breast cancer. However, few studies have information on plasma levels of hormones pre-operatively. METHODS: We studied 774 women treated for breast cancer where plasma levels of oestradiol had been measured 1-2 days pre-operatively. Date and cause of death were ascertained from the files of the Swedish Cancer Register and 5434 person-years were observed. The endpoint was death with breast cancer as the underlying cause (n=41 and n=158 in the pre- and post-menopausal group, respectively). RESULTS: In life-table analyses, only pre-menopausal patients with oestradiol 500 pmol/l and above had a tendency (not statistically significant) for better survival. Multivariate Cox models with oestradiol modelled in continuous form yielded relative hazards (RH) close to unity in all women and in strata according to menopausal status. CONCLUSIONS: When oestradiol was analysed in categorized form, only women with the highest levels had a tendency for improved prognosis (RH around 0.7; not statistically significant). Moreover, this pattern was not apparent for pre-menopausal women. Our findings contradict the notion that the pre-operative oestradiol level is independently associated with breast cancer prognosis.

Adult↗

Literature review of surgical management of abdominal aortic aneurysm.

OBJECTIVES: To review the natural history and the outcome of surgical repair of aortic abdominal aneurysm (AAA). DESIGN: An English and Scandinavian language search of papers between 1985-1997. RESULTS: After review, 132 papers with 54 048 patients remained. The mean postoperative mortality (30 days or in-hospital) for elective repair was approximately 5% and for emergency operations 47% (range 27-69%), both with significant heterogeneity. Results did not improve over time. Increasing age, presence of renal failure and atherosclerotic cardiac disease were identified as pre-operative risk factors. AAA expansion averaged 0.2-0.4 cm per year for aneurysms smaller than 4 cm, 0.2-0.5 cm for aneurysms 4-5 cm and 0.3-0.7 cm for those larger than 5 cm. The rupture risk at four years was 2, 10 and 22% respectively. The overview revealed several methodological problems in the reported studies. CONCLUSIONS: The results can be used as the basis of quality assurance or in decision trees or other models. Better reporting standards are needed.

Adolescent↗

Satisfaction with routine follow-up visits to the physician--the needs of patients with breast cancer.

Follow-up visits after surgery for breast cancer constitute a large proportion of the outpatient consultations at surgical and oncological clinics. The reasons for the follow-ups include early detection of relapse, patients' well-being, and data collection for quality assurance and scientific studies. The aim of this study was to describe the needs of the patient with breast cancer and satisfaction with routine follow-up visits to the physician. A strategic sample of 20 women with breast cancer, routinely followed-up at an oncology outpatient clinic, was interviewed. A qualitative descriptive design inspired by the phenomenographic method was used. The results identified the need for routines, accessibility, security, continuity, confidence and information. The women's views demonstrated that there are strong reasons for reviewing and changing the design of the traditional follow-up system to obtain the most effective and well-functioning system possible to better meet these women's needs.

Adult↗

Risk factors for male breast cancer--a case-control study from Scandinavia.

We report a population-based case-control study on risk factors for male breast cancer. Data on a broad range of previously suggested risk factors were collected in a set of Scandinavian breast cancer cases and matched controls. Incident cases (n = 282) with histologically verified carcinomas of the breast were identified from notification to the cancer registries of Denmark, Norway and Sweden over a 4-year period 1987-1991 and of these cases, 156 men could be approached and responded. Controls were identified through national central population registers and were matched individually for country, sex and year of birth. Controls with a diagnosis of breast cancer were excluded; 468 of 780 controls responded. Data on risk factors were collected by self-administered questionnaires mailed to the cases between land 2 years after diagnosis and to controls during the same period. The findings were compatible with an increased risk associated with family history of breast cancer (odds ratio (OR) = 3.3, 95% confidence interval (CI) 2.0-5.6), obesity 10 years before diagnosis (OR = 2.1, 95% CI 1.0-4.5) for BMI > 30, diabetes (OR = 2.6, 95% CI 1.3-5.3) and the use of digoxin and methyldopa (OR = 2.0 and 2.1, respectively). The association with family history of breast cancer has been repeated in several studies, while the relation to anthropometric measures has been equivocal. We could not substantiate some associations seen in other studies; namely those with high education, fertility, marital status, testicular injury, liver disease and religion. The detailed questions about gynaecomastia indicated that many cases reported signs of breast cancer as a gynaecomastia. This type of misunderstanding may explain the strong association with gynaecomastia seen in other studies. Several patients died before contact. Thus, risk factors related to a more aggressive male breast cancer or related to high risk of dying (e.g. liver cirrhosis, heavy smoking) may have been missed.

Anthropometry↗

Coffee consumption and risk of colorectal cancer in a population based prospective cohort of Swedish women.

BACKGROUND: The presumed protective effect of coffee consumption on colorectal cancer, which is supported by case control studies, has not been confirmed in prospective cohort studies. Cohort studies are few in number however and often suffer from a small number of cases, limited attention to confounding variables, and a low percentage of heavy coffee drinkers. METHODS: We examined data from a large population based cohort of Swedish women who were free from cancer at the start of follow up, with a wide range of coffee consumption, information on many potentially confounding variables, and a larger number of cases than any previous cohort study of coffee consumption and colorectal cancer. RESULTS: During an average of 9.6 years of follow up of 61 463 women aged 40-74 years, we observed 460 incident cases of colorectal cancer (291 with colon cancer, 159 with rectal cancer, 10 with cancer at both sites). We found no association between coffee consumption and colorectal cancer risk. The risk ratio for drinking four or more cups per day compared with none was 1.04 (95% confidence interval 0.63-1.69; p for trend 0.84). The findings were similar for cancers of the distal and proximal colon and rectum. CONCLUSIONS: The recently published affirmative conclusions regarding the protective effect of coffee consumption may be premature. For patients seeking advice about coffee consumption, the evidence suggests that moderate or even high consumption will probably not influence the risk of colorectal cancer.

Adult↗

Risk factors for subsequent invasive breast cancer and breast cancer death after ductal carcinoma in situ: a population-based case-control study in Sweden.

In a case-control study derived from a cohort of 4661 women with a primary carcinoma in situ of the breast, we investigated age at diagnosis, mode of detection, tumor characteristics, and primary therapy, as prognostic factors for developing invasive breast cancer or dying from breast cancer. From all of the women with a primary carcinoma in situ reported to the Swedish Cancer Registry from 1960 through 1992, we selected as cases all of the women with a ductal carcinoma in situ who later died of breast cancer (n = 39) or who developed a subsequent invasive cancer in either breast (n = 118). From this cohort, we also selected controls matched to the cases by year of diagnosis and health care region. We conducted univariate and multivariate analyses to study the association between risk of invasive cancer or death and the different risk factors. Large size, diameter > or = 25 mm [odds ratio (OR), 3.5; 95% confidence interval (CI), 1.1-11.4] and multifocality (OR, 3.9; 95% CI, 1.2-12.7) increased the risk of breast cancer death in univariate analysis. Postoperative radiotherapy (OR, 0.1; 95% CI, 0.0-1.0) and mastectomy (OR, 0.1-95% CI, 0.0-0.5) lowered the risk of an ipsilateral invasive cancer in multivariate analysis. The risk pattern by treatment category differed between those who had an ipsilateral invasive cancer and those who either had a contralateral cancer or died from breast cancer. The driving forces behind local and generalized disease may differ. Because confounding by indication may influence the effects of different treatments, the results should be interpreted with caution.

Adult↗

Fetal tissue banking for transplantation: characteristics of the donor population and considerations for donor and tissue screening.

We initiated this study to evaluate the suitability for therapeutic use in transplantation of tissues obtained from human abortuses. We have developed protocols for the collection, handling and preservation of hepatic stem cells from electively aborted embryos and have developed methods for assessment of the cells so derived and processed. In this paper we present our findings regarding screening of potential donors, acquisition of fetal tissues, and assessment of the tissues for potentially infectious contaminants. We assess the suitability of the tissue donors according to current standards used for donors of commonly transplanted tissues (e.g., bone grafts, skin grafts and heart valves) and present data regarding the real availability of tissues from elective abortion procedures that would meet those standard tissue banking criteria.We specifically evaluated the donor's willingness to provide a blood sample for testing, conducted a detailed interview similar to those used for typical organ and tissue donors, and assessed the type and incidence of contamination in collected tissues. We find that although many women are willing to consent to use of the tissues for transplantation, attrition from the study for various reasons results in few fetal organs ultimately realistically available for transplantation. Typical reasons for attrition include: unwillingness to have a blood sample drawn or tested, positive serology results, social/medical high risk factors for acquisition of transmissible disease, no identifiable organs available, and unacceptable microbial contamination. Thus, although it might seem that due to the numbers of abortions performed annually, that there would be substantial numbers of suitable tissues available, only a small proportion are truly suitable for transplantation.

Journal Article↗

Follow-up of prostate cancer patients by on-demand contacts with a specialist nurse: a randomized study.

OBJECTIVE: The effectiveness of traditional follow-up programs and the intensive search for disease progression in men with prostate cancer have been questioned. The aims of this randomized multi-centre study were to evaluate medical safety, patient satisfaction and resource utilization in an on-demand follow-up by a specialist nurse compared with traditional follow-up by a urologist. MATERIAL AND METHODS: Four hundred consecutively approached men with newly diagnosed or previously known prostate cancer in any stage at three hospitals in Sweden were randomized to follow-up in the nurse group (NG, 200 patients) or the urologist group (UG, 200 patients). In the NG, the nurse contacted the patient by phone every 6 months unless the patient himself initiated the contact. Patient satisfaction was evaluated twice a year via questionnaire. The questionnaire included the validated Hospital Anxiety and Depression Scale (HADS). The costs of all medical interventions and adverse events related to prostate cancer were calculated for all patients. RESULTS: Medical safety, measured as complication frequency and lag time from symptoms to intervention, during the first 3 years of the observation period, was similar in the NG and the UG. The total number of interventions due to symptoms from prostate cancer was also similar in both groups. The analysis of accessibility and the HAD scale showed no significant differences between the groups. The mean outpatient cost (excluding pharmaceutical costs) per patient was lower in the NG compared to the UG, especially among patients without metastases at inclusion (37% lower cost). CONCLUSIONS: Our study indicates that men with prostate cancer can be safely followed up by a specialist nurse. The study results show that this alternative follow-up is cost-effective, especially in men without metastases.

Aged↗

Pilot trial of cytoprotection with amifostine given with high-dose chemotherapy and autologous peripheral blood stem cell transplantation.

In an attempt to limit toxicities associated with dose-intensive therapy used for transplant regimens, we performed a pilot study using amifostine with high-dose busulfan (12 mg/kg), melphalan (100 mg/m2), and thiotepa (500 mg/m2) in 21 patients with a variety of malignancies. After 3 days of oral busulfan, amifostine was given at 910 mg/m2 IV for 10 minutes, preceding the infusion of each of 2 doses of melphalan and thiotepa given for 4 days. Antiemetic premedication for amifostine was given to all patients. The median patient age was 50 years (range: 32-65 years). Twenty-one patients received 82 separate amifostine infusions. One patient discontinued amifostine after the second dose because of severe nausea and emesis, and two infusions were temporarily held secondary to hypotension. Of these 82 cycles, there was a total of 37 episodes of nausea/vomiting, 28 episodes of sneezing, 11 episodes of flushing, and 1 episode of oral paresthesia. Systolic blood pressure and mean arterial pressure decreased by a mean of 8.4 mm Hg and 5.0 mm Hg, respectively. In general, the infusion was well tolerated. Patients were observed until discharge home (N = 15), until initiation of an additional tandem transplant procedure (N = 4), or until death (N = 2). All twenty-one patients experienced nonhematologic toxicities grade II or greater. Grade II toxicities included mucositis (N = 21), gastrointestinal (N = 3), skin (N = 1), and liver (N = 1), and grade III toxicities included liver (N = 1). Mucositis was also scored according to a detailed toxicity assessment. Mucositis did not appear to be improved with amifostine when compared with a control group of patients not receiving amifostine. Renal dysfunction after transplantation was decreased in the amifostine group, whereas there was no significant effect on posttransplant hepatic dysfunction. Although these data demonstrate the feasibility of delivering parenteral amifostine in conjunction with dose-intensive chemotherapy and autologous peripheral blood stem cell transplantation, there was no evidence of a significant reduction in nonmarrow toxicities.

Adult↗

Release of ribosome-bound 5S rRNA upon cleavage of the phosphodiester bond between nucleotides A54 and A55 in 5S rRNA.

Reticulocyte lysates contain ribosome-bound and free populations of 5S RNA. The free population is sensitive to nuclease cleavage in the internal loop B, at the phosphodiester bond connecting nucleotides A54 and A55. Similar cleavage sites were detected in 5S rRNA in 60S subunits and 80S ribosomes. However, 5S rRNA in reticulocyte polysomes is insensitive to cleavage unless ribosomes are salt-washed. This suggests that a translational factor protects the backbone surrounding A54 from cleavage in polysomes. Upon nuclease treatment of mouse 60S subunits or reticulocyte lysates a small population of ribosomes released its 5S rRNA together with ribosomal protein L5. Furthermore, rRNA sequences from 5.8S, 28S and 18S rRNA were released. In 18S rRNA the sequences mainly originate from the 630 loop and stem (helix 18) in the 5' domain, whereas in 28S rRNA a majority of fragments is derived from helices 47 and 81 in domains III and V, respectively. We speculate that this type of rRNA-fragmentation may mimic a ribosome degradation pathway.

Animals↗