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Biomedical subjects

C Ingvar

Publications and source records attributed to C Ingvar.

At least 37 records · Page 2Linked to original sources
PubMed1996

Correlation between karyotypic pattern and clincopathologic features in 125 breast cancer cases.

A correlation analysis was performed on 125 cytogenetically characterized breast cancer cases to assess the relationship between the tumor karyotype and clinicopathologic features. The carcinomas of young women had a higher modal chromosome number than those of older women. The number of chromosomal aberrations and modal chromosome number were also found to correlate with the histologic type, grade and mitotic activity of the tumor. Whereas all lobular carcinomas were karyotypically normal or near-diploid, more than 3 aberrations and sometimes near-triploid or near-tetraploid karyotypes were common findings in ductal carcinomas, especially in grade-III tumors and in tumors showing high mitotic activity in vivo. Karyotypes with cytogenetically unregulated clones and unbalanced structural chromosomal rearrangements were more frequent in infiltrating than in in situ carcinomas but, at least as far as the second of these 2 characteristics is concerned, especially in infiltrating carcinomas that also had an in situ component. The presence of cytogenetic polyclonality correlated with tumor grade. Although recurrent chromosome aberrations were significantly more common in ductal than in lobular carcinomas, none of these breast cancer-associated anomalies seemed to be specific for any particular clinicopathologic parameter. The associations between modal chromosome number and mitotic activity and between cytogenetic polyclonality and tumor grade were found to be statistically significant in multivariate models. No correlations was seen between the karyotypic findings and tumor size or the presence of axillary-lymph-node metastases.

Adult↗
PubMed1996

Chromosome aberrations in prophylactic mastectomies from women belonging to breast cancer families.

Short-term cultures of samples from eight prophylactic mastectomies from five unrelated women who were genetically predisposed to breast cancer were analyzed cytogenetically. Clonal chromosome abnormalities were detected in five breasts. Three samples from two women had aberrations involving the short arm of chromosome 3, with a breakpoint in 3p14 in common. Three samples from three women had rearrangements of 1q. Two of them, one of which also displayed a 3p14 rearrangement, shared a breakpoint in 1q41. Both 1q41 and, in particular, 3p14 have been reported to be rearranged frequently in malignant breast proliferations. Whether alterations of genes in these bands are essential in mammary tumorigenesis and, if so, whether they are equally important in sporadic and in hereditary cases remains to be explored.

Adult↗
PubMed1996

Proliferation of the breast epithelium in relation to menstrual cycle phase, hormonal use, and reproductive factors.

The proliferative rate in normal breast epithelium from 58 women undergoing reduction mammoplastics was studied using the formalin resistant antibody Ki-S5, and related to age at operation, menstrual cycle phase, family history of breast cancer, height and weight, parity, and hormonal use. The breast tissue from women operated on in the luteal menstrual cycle phase (day 15-28 among oral contraceptive (OC) users) had significantly higher proliferative rate than breast tissue removed from women in the follicular phase (day 1-14) (p = 0.01). Among women presently exposed to hormones, those with a positive family history of breast cancer among first and second degree relatives had significantly higher values than cases without such history (p = 0.02). Weight was not significantly related to proliferation rate, while a short height was associated with a significantly higher proliferation rate (p = 0.04). Women who used OCs before the first full-term pregnancy (FFTP) had a significantly higher proliferation rate compared with never users or late users (p = 0.04). No significant difference was seen between parous versus nulliparous women. The results from the univariate analysis persisted in multivariate models. An especially high proliferation rate was seen in young women with both a positive family history and present hormonal use (p = 0.001). Overall, it was found that young women had a non-significantly higher proliferation rate than older women (p = 0.10). Due to small sample size, these results must be regarded as preliminary, especially in the subgroup analyses.

Adolescent↗
PubMed1996

Risk of malignant melanoma in relation to drug intake, alcohol, smoking and hormonal factors.

In a population-based, matched case-control study from southern Sweden of 400 patients with a first diagnosis of malignant melanoma and 640 healthy control subjects aged 15-75 years, the association between commonly prescribed drugs, alcohol, smoking and malignant melanoma was evaluated. In addition, the relation between reproductive and hormonal factors and melanoma in women was studied. It was found that certain specific types of prescribed drugs, i.e. beta-blockers, hydralazines and benzodiazepines, may increase the risk of melanoma development. However, these associations were diminished, at least for benzodiazepines, after controlling for host factors. As these findings are unconfirmed, and may be due to chance or confounding, further studies are warranted. The risk of malignant melanoma was not influenced by alcohol consumption or smoking habits. Our results do not suggest an association between oral contraceptives and melanoma. Furthermore, reproductive factors were not independent risk factors for melanoma. However, increasing number of live births seemed to be protective (P for trend = 0.01). There is a need for further research to be able to draw firm conclusions on the relation between number of live births and melanoma. The results based on histopathological re-examinations and those based on tumour registry data were essentially the same.

Adolescent↗
PubMed1996

Reproducibility of a self-administered questionnaire for assessment of melanoma risk.

BACKGROUND: The reproducibility of a self-administered questionnaire on different epidemiological variables was examined in a random sample of a cohort of healthy women from the South Swedish Health Care Region. An identical questionnaire has previously been used for assessment of melanoma risk, in a population-based, matched, case-control study from the same region. METHODS: Repeat questionnaires were completed on two occasions, 1-3 years apart, by 670 randomly selected subjects. In addition, exposure data from a case-control study were used to estimate the effect of misclassification. RESULTS: Overall, there was a fair to good consistency between the answers on the two occasions for the various epidemiological variables. Exposure variables identified as risk factors for melanoma development were reasonably reproducible. The estimated proportion of agreement, A, ranged from 0.74 to 0.92, the average correct classification rate (assuming common sensitivity and specificity), pi, was > or = 0.85 and the kappa coefficient, kappa, ranged between 0.52 and 0.83. However, the question on number of raised naevi on the arm was an exception since it had a lower test-retest reliability (A = 0.62, pi = 0.77, kappa = 0.40). When using data from the case-control study, the effect of the estimated random misclassification was found to only slightly bias odds ratios toward one. CONCLUSION: Our questionnaire, used for assessment for melanoma risk, provided information with fair to good test-retest reliability, and corrected odds ratios were found to be only slightly higher than observed odds ratios.

Adolescent↗
PubMed1996

A sensitivity and specificity analysis of the surface microscopy features of invasive melanoma.

In vivo cutaneous surface microscopy, epiluminescence microscopy, dermoscopy, dermatoscopy and magnified oil immersion diascopy, are terms that describe the use of an incident light magnification system to examine cutaneous lesions, usually with immersion oil at the skin-microscope interface. The result is the visualization of a multitude of morphological features, not visible with the naked eye, that enhance the clinical diagnosis of nearly all pigmented lesions. Sixty-two invasive melanomas and 159 randomly selected non-melanoma pigmented lesions were used in the study. The non-melanomas, while randomly selected from a large data base, were all clinically atypical. Using the x 10 magnification of hand-held surface microscopes (Dermatoscope, Episcope), we present an analysis of 72 surface microscopic variables (constituting over 15,000 single observations) for the diagnosis of invasive melanoma. Forty of the 72 features studied were shown to differ significantly between invasive melanoma and non-melanoma pigmented lesions. Blue-white veil, multiple brown dots, radial streaming and pseudopods had a specificity greater than 95% for melanoma. Two features, symmetrically irregular pigment (non-uniform pigmentation with point and axial symmetry) and the presence of a single colour, had a sensitivity of 0%, i.e. were absent, in melanoma. The other significant features are presented, with their sensitivity and specificity for melanoma.

Humans↗
PubMed1996

Determinants of acute regional toxicity following isolated limb perfusion for melanoma.

Hyperthermic isolated limb perfusion (ILP) with melphalan is well established as an effective form of treatment for recurrent melanoma confined to an extremity. High drug concentrations in the limb are readily achieved, without systemic side-effects. However, regional toxicity can lead to considerable morbidity and functional disturbance. This study was undertaken to evaluate factors which might contribute to acute regional toxicity following ILP. Melphalan concentrations in limb blood samples taken at regular intervals during 135 ILPs were measured by HPLC, allowing peak melphalan concentration and area under the curve (AUC) for each procedure to be determined. Acute regional toxicity associated with ILP was found to be significantly correlated with limb tissue temperatures > 40 degrees C, peak melphalan concentration and melphalan AUC, in decreasing order, but was not correlated with tourniquet time. Further studies are required to directly assess melphalan uptake by tumour tissue, and to relate this to both limb toxicity and tumour response.

Antineoplastic Agents, Alkylating↗
PubMed1996

Dynamic indium-111-pentetreotide scintigraphy in breast cancer.

UNLABELLED: The efficacy of imaging breast cancer with 111In-pentetreotide (somatostatin receptor scintigraphy) was evaluate before surgery. METHODS: Seventy-one whole-body scintigrams in 24 patients with known breast cancer and 24 whole-body scintigrams in 8 controls were obtained at 0.5, 5 and 24 hr after intravenous injection of 110 MBq 111In-pentetreotide. Anterior and posterior projection images were acquired simultaneously. SPECT of the thorax was performed at 5 or 24 hr after injection in all breast cancer patients. The specimens were imaged immediately after surgery and the distribution of pentetreotide was assessed qualitatively and quantitatively. RESULTS: Somatostatin receptor-positive tumors were found in 18/24 patients with breast cancer. Pentetreotide uptake was significantly greater in breast cancer patients compared to control patients. In all patients with positive images, the early scintigram (0.5 hr) showed abnormal uptake. It was possible to delineate three different dynamic patterns. Increased uptake was visually most distinct at each time (9 patients). Moreover, bilaterally increased pentetreotide uptake was observed in 10/18 true-positive patients (in 8 at each time and in 2 patients only at 5 hr), but only one patient had a known bilateral tumor. CONCLUSION: We found higher incidence of somatostatin receptors in patients with breast cancer than in the control group. Moreover, bilaterally increased pentetreotide uptake in clinically unilateral disease was an unexpected finding.

Breast Neoplasms↗
PubMed1996

Frequency and morphologic characteristics of invasive melanomas lacking specific surface microscopic features.

OBJECTIVES: To create a simple diagnostic method for invasive melanoma with in vivo cutaneous surface microscopy (epiluminescence microscopy, dermoscopy, dermatoscopy) and to analyze the incidence and characteristics of those invasive melanomas that had no diagnostic features by means of hand-held surface microscopes. DESIGN: Pigmented skin lesions were photographed in vivo with the use of immersion oil. All were excised and reviewed for histological diagnosis. A training set of 62 invasive melanomas and 159 atypical nonmelanomas and a test set of 45 invasive melanomas and 119 atypical non-melanomas were used. Images from the training set were scored for 72 surface microscopic features. Those features with a low sensitivity (0%) and high specificity (> 85%) were used to create a simple diagnostic model for invasive melanoma. SETTING: All patients were recruited from the Sydney (Australia) Melanoma Unit (a primary case and referral center). PATIENTS: A random sample of patients whose lesions were excised, selected from a larger database. MAIN OUTCOME MEASURES: Sensitivity and specificity of the model for diagnosis of invasive melanona. RESULTS: The model gave a sensitivity of 92% (98/107) and specificity of 71%. Of the 9 "featureless" melanomas the model failed to detect, 6 were pigmented and thin and had a pigment network. The other 3 were thicker, hypomelanotic lesions lacking a pigment network, some with prominent telangiectases, and all with only small areas of pigment. All featureless melanomas noted by the patients had a history of change in color, shape, or size. CONCLUSIONS: Surface microscopy does not allow 100% sensitivity in diagnosing invasive melanoma and therefore cannot be used as the sole indicator for excision. Clinical history is an important consideration when featureless lesions are diagnosed.

Algorithms↗
PubMed1995

Chromosome analysis of 97 primary breast carcinomas: identification of eight karyotypic subgroups.

Chromosome banding analysis of 97 short-term cultured primary breast carcinomas revealed clonal aberrations in 79 tumors, whereas 18 were karyotypically normal. In 34 of the 79 tumors with abnormalities, two to eight clones per case were detected; unrelated clones were present in 27 (34%) cases, whereas only related clones were found in seven. These findings indicate that a substantial proportion of breast carcinomas are of polyclonal origin. Altogether eight abnormalities were repeatedly identified both as sole chromosomal anomalies and as part of more complex karyotypes: the structural rearrangements i(1)(q10), der(1:16)(q10;p10), del(1)(q11-12), del(3)(p12-13p14-21), and del(6)(q21-22) and the numerical aberrations +7, +18, and +20. At least one of these changes was found in 41 (52%) of the karyotypically abnormal tumors. They identify a minimum number of cytogenetic subgroups in breast cancer and are likely to represent primary chromosome anomalies in this type of neoplasia. Other candidates for such a role are translocations of 3p12-13 and 4q21 with various partner chromosomes and inversions of chromosome 7, which also were seen repeatedly. Additional chromosomal aberrations that give the impression of occurring nonrandomly in breast carcinomas include structural rearrangements leading to partial monosomies for 1p, 8p, 11p, 11q, 15p, 17p, 19p, and 19q and losses of one copy of chromosomes X, 8, 9, 13, 14, 17, and 22. The latter changes were seen consistently only in complex karyotypes, however, and we therefore interpret them as being secondary anomalies acquired during clonal evolution.

Breast Neoplasms↗
PubMed1995

Is the use of sunscreens a risk factor for malignant melanoma?

The relation between use of sunscreens, different host factors and malignant melanoma was investigated in a population-based, matched case-control study of malignant melanoma in the South Swedish Health Care Region, which has the highest risk for melanoma in Sweden, between 1 July 1988 and 30 June 1990. In total, 400 melanoma patients and 640 healthy controls aged 15-75 years answered a comprehensive questionnaire regarding different epidemiologic variables, including questions on use of sunscreens and different constitutional factors. The use of sunscreens was not found to protect against developing malignant melanoma. Instead, an unexpected relation between the use of sunscreens and the risk of developing malignant melanoma was seen (odds ratio (OR) 1.8 for almost always vs never using sunscreens). A tentative dose-response relation was found. Virtually the same ORs were seen in both sexes. Furthermore, persons younger than 50 years had a higher OR than persons older than 50 years. When different melanoma presentation sites were considered, lesions of the trunk were associated with sunscreen use in females (adjusted OR = 3.7 for almost always vs never using sunscreens), while lesions of the extremity or head and neck were associated with sunscreen use in males (adjusted OR = 3.2 for almost always vs never using sunscreens). Raised naevi on the left arm and freckling were shown to be the major constitutional risk factors (OR = 3.9 for more than three naevi vs none and OR = 1.4, respectively). The results were essentially unaltered in a histopathologically re-examined material. Further investigations are needed in order to form a basis for melanoma prevention.

Adolescent↗
PubMed1995

Induction of primary antigen-specific immune reponses in SCID-hu-PBL by coupled T-B epitopes.

Adoptive transfer of human lymphoid cells into immunodeficient (SCID) mice lacking the ability to functionally rearrange T- and B-cell receptor genes constitutes a unique model to study and manipulate human immunocytes. We have investigated this model for the purpose of generating an antigen-specific primary humoral immune response. Peripheral blood lymphocytes (PBL) derived from blood donors were used to repopulate SCID mice, which subsequently were immunized with different B-cell epitopes coupled to either tetanus toxoid (TT), or to a promiscuous helper epitope of TT, or by incorporating the antigens into a liposome construct. By recruiting the necessary T-cell help found in the T-cell memory compartment against TT, primary immune responses were obtained against the hapten dinitrophenyl (DNP), the V3 loop peptide derived from glycoprotein (gp120) (HIV-1), the melanoma-associated GD2 ganglioside and ovine submaxillary mucin. The primary immune response against the GD2 ganglioside was induced by incapsulating TT into GD2-containing liposomes. These liposome constructs also allowed us to induce a high human IgG serotitre (3000-4000) against this normally not very immunogenic ganglioside.

Animals↗
PubMed1995

Dynamic Octreotide scintigraphy in neuroendocrine tumours.

The purpose of the present study was to investigate the optimal time for scintigraphy after injection of the radio-labelled somatostatin analogue, Octreotide. A secondary purpose was to evaluate the value of SPECT. One SPECT study and up to 4 whole body scans were performed in 22 patients with neuroendocrine tumours 0.5, 5, 24 and 48 hours after an injection of 110 MBq In-DTPA Octreotide. A total of 98 scintigrams were studied. A pathological uptake was found in 19 of the 22 patients. In 3 cases, early scintigrams (0.5 and 5 hours after injection) were of the most value whereas late scintigrams (24 and 48 hours) were the best in 4 cases. SPECT was found to be of value in 13 of 21 cases. For correct interpretation of Octreotide scintigraphy it is necessary to obtain both early and late scintigrams as well as a SPECT study.

Adult↗
PubMed1994

Use of sunbeds or sunlamps and malignant melanoma in southern Sweden.

In a population-based, matched case-control study from the South Swedish Health Care Region, which has the highest risk for melanoma in Sweden, the relation between the use of sunbeds or sunlamps and malignant melanoma was investigated. Between July 1, 1988, and June 30, 1990, a total of 400 melanoma patients and 640 healthy controls aged 15-75 years answered a comprehensive questionnaire containing different epidemiologic variables. Questions regarding the use of sunbeds or sunlamps were included. The odds ratio for developing malignant melanoma after ever having used sunbeds or sunlamps was 1.3. Considering all age groups, the odds ratio was significantly elevated after exposure more than 10 times a year to sunbeds or sunlamps (odds ratio (OR) = 1.8). When the study was restricted to patients and controls younger than age 30 years because the use of tanning devices is much more common among young persons, the odds ratio was higher (OR = 7.7 for more than 10 times a year vs. none). These findings were independent of constitutional factors and factors regarding sun exposure. A dose-response relation was evident. Furthermore, among melanoma patients in this young age group, the ratio of females to males was significantly higher than in older patients. When different melanoma presentation sites were considered, only lesions of the trunk were significantly associated with sunbed or sunlamp use (OR = 4.2 for more than 10 times a year vs. none).

Adolescent↗
PubMed1994

Cutaneous malignant melanoma in south Sweden 1965, 1975, and 1985. A histopathologic review.

BACKGROUND: There is an increase in the incidence of cutaneous malignant melanoma (CMM) among white people throughout the world. In Sweden, a fivefold increase has been recorded since 1960, but the mortality is rising at a much lower rate. Tumor thickness is the single most important prognostic factor for primary melanoma. This study aimed to clarify whether the thickness of the tumor in invasive CMM decreased during the period 1965-1985. METHODS: This population-based study identified 574 cases of CMM, both invasive and noninvasive, in the South Swedish Health Care Region in 1965, 1975, and 1985. Twenty-six cases were excluded because the collection or evaluation of the material was not possible. The remaining 548 cases were reviewed histopathologically, and a diagnosis of invasive CMM was rejected in 71 cases. Eventually, 467 cases of invasive melanoma remained in our study (70 in 1965, 124 in 1975, and 273 in 1985). The level of invasion, tumor thickness, regression, ulceration, presence of inflammatory cells, benign naevus cells, and the site of presentation were studied. RESULTS: The study found neither a significant decrease of tumor thickness of invasive CMM nor changes in the level of invasion or proportion of ulcerated melanoma. A significantly higher proportion of melanoma tumors containing benign naevus cells was seen throughout the years (P < 0.05). Women had significantly fewer inflammatory cells in their tumors than did men (P < 0.01). As expected, the anatomical site of presentation showed a significant sex-related difference, with more tumors on the legs of female patients and more on the trunk of male patients (P < 0.001). CONCLUSIONS: There is a divergence between the rapidly increasing incidence and the slower increase in mortality of CMM. This cannot be explained by a removal of the melanoma at a thinner thickness. Differences between the sexes according to the tumor site and the increasing rate of CMM containing benign naevus cells could implicate changes in the tumor biology. Public education in Sweden concerning ultraviolet radiation and the connection with melanoma is fairly new and might not have any influence on this time period. Additional investigation is needed to clarify this matter.

Adolescent↗
PubMed1994

At what age do sunburn episodes play a crucial role for the development of malignant melanoma.

The age relationship between sunburns and malignant melanoma was investigated in a population-based, matched, case-control study from the South Swedish Health Care Region (the highest risk area for melanoma in Sweden). Between 1988 and 1990, a total of 400 patients with a first diagnosis of malignant melanoma and 640 healthy controls aged 15-75 years answered a comprehensive questionnaire including questions regarding ultraviolet radiation exposure. In addition, a literature review was performed. The average number of episodes of sunburn per year was significantly associated with malignant melanoma (relative risk, RR = 1.9 for > or = three episodes per year versus never). Outdoor employment during the summer was associated with a decreased risk for the development of malignant melanoma (RR = 0.8). Data from case-control studies and migration studies concerning age relationship between sunburns and melanoma are inconsistent. From our own data, we did not find a higher risk of melanoma developed in individuals who had experienced severe sunburns in childhood. Instead, a significantly increased risk was associated with sunburns after age 19 years, RR = 2.2 for a history of more than five times versus never. Even if the hypothesis is biologically plausible, that episodes of sunburn early in life are associated with a higher risk of melanoma, so far epidemiological evidence is scarce. There is a need for better prospective epidemiological studies addressing this issue.

Adolescent↗
PubMed1994

Maximizing efficacy and minimizing toxicity in isolated limb perfusion for melanoma.

Isolated limb perfusion (ILP) with melphalan is an effective treatment for recurrent melanoma, but complete remission is achieved only in about 40% of patients. Regional toxicity is common, causing short-term disability and occasional longterm incapacity. Methods to maximize the efficacy and minimize the toxicity were investigated in 210 ILPs undertaken at the Sydney Melanoma Unit. Toxicity was found to be related to peak melphalan concentration, as well as to the area under the curve and maximum temperature. A dye dilution technique has been developed to measure perfusion circuit volume, so that a drug dose can be given to achieve an appropriate concentration. ILP with cisplatin was less effective and produced greater toxicity than ILP with melphalan; other drugs and drug combinations warrant investigation. Prophylactic ondansetron successfully controlled post-operative nausea and vomiting in most patients. Daily measurement of serum creatine phosphokinase (CPK) allowed early recognition of impending severe toxicity, with the greatest risk if CPK exceeded 1000 IU/l after the first post-perfusion day. Isolated limb 'infusion' (ILI) with melphalan, using percutaneously inserted catheters, is a much simpler procedure than ILP and has been found to be effective and easily repeated. The morbidity of ILP and ILI may be minimized by excluding the foot or hand with a rubber bandage.

Chemotherapy, Cancer, Regional Perfusion↗