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J Lindholm

Publications and source records attributed to J Lindholm.

At least 19 recordsLinked to original sources
PubMed2006

Growth hormone: historical notes.

A brief review of important contributions to our present knowledge of growth hormone is given. In 1887 it had been noted that a pituitary tumor was present in most patients with acromegaly. Even at the beginning of the 20. Century relationship between growth disorders and the pituitary was contested. From 1908 pituitary surgery became established treatment in GH hypersecretion. In 1922 it was demonstrated that injection of pituitary extract to animals caused excessive growth and soon after the opposite: removal of the pituitary caused growth retardation. A huge number of studies on the effects of GH were subsequently reported as were trials with GH treatment. They were impeded by failure to recognize the impact of species specificity of GH. After this issue was clarified in 1957, treatment with human growth hormone proved effective. In 1985 it was realized that Creutzfeldt-Jakob's disease might be transmitted through human growth hormone. At this time recombinant GH had become available. In 1971 the structure of human GH was established. In the same period both GH releasing and inhibiting hormones were identified and an analogue of somatostatin had evolved into the first effective pharmacological treatment for acromegaly.

Acromegaly↗
PubMed2006

Frequent occurrence of pituitary apoplexy in patients with non-functioning pituitary adenoma.

BACKGROUND AND OBJECTIVE: There is agreement in the literature that pituitary apoplexy is a rare disorder. As our experience differs from this view, we analysed the incidence in patients operated on for a nonfunctioning pituitary adenoma. PATIENTS AND DESIGN: One hundred ninety-two consecutive patients with a suprasellar, clinically inactive adenoma operated on during the period 1985-1996 were retrospectively reviewed. A diagnosis of pituitary apoplexy was made from relevant neurological symptoms together with pertinent findings at operation. RESULTS: Pituitary apoplexy occurred in 41 patients (21%), in 23 patients within 12 days prior to the operation. The male/female ratio was 1.9. Median follow-up time was 13.7 years (range 8.9-19.9). During this period, 12 patients had died, yielding a standard mortality ratio of 1.09 (95% CI 0.62-1.92), similar to that in the patients who had not sustained pituitary apoplexy. Postoperatively, 24% of the patients had normal pituitary function, 38% were panhypopituitary and partial pituitary insufficiency was present in 38%. Subnormal GH secretion was present in virtually all patients tested. Two patients died within 60 days of surgery and in two no or incomplete data were available, although they most likely were panhypopituitary. CONCLUSION: Most of our findings add little to what is known about pituitary apoplexy. On one point, however, they are contrary to previously presented data. We found a much higher incidence of pituitary apoplexy despite rather rigorous criteria for the diagnosis. The outcome as regards survival and endocrine function was not different from that in patients with a nonfunctioning adenoma who did not suffer pituitary apoplexy.

Adenoma↗
PubMed2006

Hypopituitarism and mortality in pituitary adenoma.

BACKGROUND AND OBJECTIVE: Previous studies on hypopituitarism and mortality have concluded that insufficient pituitary function is associated with decreased survival. For several reasons the results are difficult to compare - particularly because definitions and treatment of hypopituitarism have varied and various underlying disorders have been included. The purpose was to assess the relationship between mortality and pituitary function. PATIENTS AND DESIGN: One hundred and sixty consecutive patients (99 men and 61 women) with functionless, suprasellar pituitary adenoma. All were operated on transsphenoidally during the period 1985-1996. Additional radiotherapy was given to 29 patients. Mortality was calculated 12.4 years (median, range 8.1-19.9) after operation. Postoperative hormonal deficits were treated in most, though GH substitution was given only to a minority of patients. RESULTS: Postoperatively 30% of the patients had normal pituitary function (normal adrenocortical, thyroid and gonadal function), 26% were panhypopituitary and 36% had partial pituitary insufficiency. Forty-one patients had died (34.7 expected) yielding a standard mortality ratio (SMR) of 1.18 (95% confidence limits (CI) 0.87-1.60). SMR was significantly increased in women (1.97, CI 1.20-3.21) but not in men (0.83, CI 0.55-1.26). SMR in patients with normal pituitary function, panhypopituitarism and partial insufficiency were not different from that in the general population. SMR in hypopituitary women was substantially higher than in men with pituitary insufficiency. Treatment with growth hormone in GH-deficient patients did not influence survival. CONCLUSION: Pituitary surgery for nonfunctioning adenoma and subsequent pituitary insufficiency had no effect on mortality in men, but was associated with significantly increased mortality in women. Suboptimal hormonal substitution in women may play a role.

Adenoma↗
PubMed2005

Radiofrequency ablation in the liver close to the bile ducts: can intraductal cooling offer protection?

BACKGROUND: One complication of radiofrequency ablation (RFA) of the liver is biliary duct damage. Intraductal cooling (IDC) has been proposed as a means of protection. METHODS: In the first experiment, designed to evaluate the influence of IDC on the RFA procedure per se and on lesion formation, lesions were created in vivo in pig liver with and without IDC. The RFA needle was placed with a 1.5-cm safety margin from the bile ducts. In the second experiment, designed to evaluate the potential protective effects of IDC, lesions were created close to a bile duct with and without IDC. RESULTS: With the safety margin, the RFA parameters and lesion size were not negatively affected by IDC. Microscopic examination revealed that IDC had a protective effect in most of the lesions created close to a bile duct. CONCLUSIONS: The IDC procedure was feasible and had no negative effect on the RFA procedure or the lesions. However, the protective effect of IDC was not statistically significant (p = 0.12).

Animals↗
PubMed2003

Prognostic value of preoperative magnetic resonance imaging of the pelvis in rectal cancer.

BACKGROUND: Despite radiotherapy and improved surgical techniques, local recurrence rates after treatment of rectal cancer still vary between 3 and 30 per cent. Tumour involvement of the circumferential resection margin (CRM) predicts a high risk of local recurrence. Magnetic resonance imaging (MRI) allows accurate description of the tumour and its spread within the mesorectum. The aim of this study was to assess the prognostic impact of an involved CRM identified at preoperative MRI in patients with rectal cancer. METHODS: Preoperative MRI was performed in 115 patients with rectal cancer between 1995 and 1999. The images were evaluated retrospectively. The shortest distance from the tumour to the CRM was measured, correlated with patient outcome and compared with histopathological findings. RESULTS: The risk of any recurrence in patients with or without a tumour-involved margin on MRI was nine of 29 and nine of 57 respectively (P = 0.036). Overall survival at 5 years was 43 and 77 per cent (P = 0.012) respectively. Twenty-four of 30 patients who had an involved CRM on histopathology were correctly identified by MRI. CONCLUSION: Patients with a potentially involved CRM identified by MRI had a significantly higher risk of recurrence and cancer-related death. Preoperative MRI may be of prognostic value in rectal cancer and may be used to select patients for neoadjuvant radiochemotherapy and/or more radical surgery.

Adult↗
PubMed2003

Changing pattern of paediatric inflammatory bowel disease in northern Stockholm 1990-2001.

BACKGROUND: An increased incidence of paediatric Crohn's disease was reported recently by our group. AIMS: To assess the incidence and characteristics of inflammatory bowel disease (IBD) in northern Stockholm between 1990 and 2001. METHODS: All records of individuals 0-15 years of age with suspected IBD in the population based catchment area of 180000 individuals were scrutinised using defined diagnostic criteria. Patient files were searched for relatives with IBD, and for concomitant autoimmune diseases. RESULTS: A total of 152 children were diagnosed with IBD, corresponding to an overall incidence (per 100000) of IBD of 7.4. The incidence of Crohn's disease (CD) was 4.9, ulcerative colitis (UC) 2.2, and indeterminate colitis 0.2. Between 1990 and 2001, there was a marked increase in the incidence of CD while the incidence of UC was almost unchanged, leading to a net increase in the overall occurrence of IBD. There was a male dominance of CD. Fourteen per cent and 11% of patients with CD and UC, respectively, had a first or second degree relative with IBD. Eighteen per cent and 10% of patients with CD and UC, respectively, had a concomitant autoimmune disease. Ten patients with CD (10%) underwent surgery. CONCLUSIONS: The incidence of CD has increased in northern Stockholm. The current incidence is higher than that reported from other areas. Our results suggest a shift in presentation and diagnosis from UC towards CD, but also a net increase in IBD. Concomitant autoimmune disorders and family history are common in paediatric IBD.

Autoimmune Diseases↗
PubMed2002

Cryptal lymphocytic coloproctitis: a new phenotype of lymphocytic colitis?

BACKGROUND/AIMS: Lymphocytic colitis is a clinicopathological entity characterised by protracted watery diarrhoea and an increased number of intraepithelial lymphocytes (IELs) in the surface epithelium of the colonic mucosa. This report describes two patients with symptoms similar to those of lymphocytic colitis and an increased number of IELs, but within the cryptal epithelium. METHODS: The numbers of IELs were assessed in colorectal biopsies from the two patients. Sections were stained immunohistochemically for CD3, CD8, CD20, and TIA1. RESULTS: The colorectal biopsies had an abnormally high number of IELs in the epithelium of the crypts but not in the surface epithelium. The IELs in the crypts were CD3+++, CD8+, TIA1+, and CD20-. CONCLUSIONS: The histological diagnosis in these two patients was cryptal lymphocytic coloproctitis. Patients with similar symptoms and an increased number of IELs in the surface epithelium are now filed at this department as having surface lymphocytic coloproctitis. Immunohistochemistry showed that the cryptal IELs were cytotoxic suppressor T cells. Interestingly, a case of cryptal lymphocytic colitis was recently recorded in a non-human primate dying after years of protracted chronic diarrhoea. It is possible that antigens present in the lumen of the crypts elicit a lymphocytic reaction within the cryptal cells.

Adult↗
PubMed2001

Incidence and late prognosis of cushing's syndrome: a population-based study.

The main purpose was to assess the incidence and late outcome of Cushing's syndrome, particularly in Cushing's disease. Information for all patients diagnosed with Cushing's syndrome during an 11-yr period in Denmark was retrieved. The incidence was 1.2-1.7/million.yr (Cushing's disease), 0.6/million.yr (adrenal adenoma) and 0.2/million.yr (adrenal carcinoma). Other types of Cushing's syndrome were rare. In 139 patients with nonmalignant disease, 11.1% had died during follow-up (median, 8.1 yr; range, 3.1-14.0), yielding a standard mortality ratio (SMR) of 3.68 [95% confidence interval (CI), 2.34-5.33]. The SMR was partly attributable to an increased mortality within the first year after diagnosis. Eight patients died before treatment could be undertaken. The prognosis in patients with malignant disease was very poor. Patients in whom more than 5 yr had elapsed since initial surgery were studied separately, including a questionnaire on their perceived quality of health. In 45 patients with Cushing's disease who had been cured through transsphenoidal neurosurgery, only 1 had died (SMR, 0.31; CI, 0.01-1.72) compared with 6 of 20 patients with persistent hypercortisolism after initial neurosurgery (SMR, 5.06; CI, 1.86-11.0). In patients with adrenal adenoma, SMR was 3.95 (CI, 0.81-11.5). The perceived quality of health was significantly impaired only in patients with Cushing's disease and appeared independent of disease control or presence of hypopituitarism. It is concluded that 1) Cushing's syndrome is rare and is associated with increased mortality, in patients with no concurrent malignancy also; 2) the excess mortality was mainly observed during the first year of disease; and 3) the impaired quality of health in long-term survivors of Cushing's disease is not fully explained.

Adolescent↗
PubMed2000

Cushing's syndrome: historical aspects.

A brief overview of the most important steps leading to our present knowledge of hypercorticism is given. The adrenals were described in 1563 and the pituitary had been known since Antiquity. Until Addison's description of adrenal insufficiency in 1855 virtually nothing was known of their function. Cushing in 1912 described his famous patient with hypercorticism but assumed it to be a polyglandular disorder. For almost 40 years the etiology was disputed, though Bauer early had postulated that hypercorticism ultimately reflected adrenal hyperfunction, either primarily or secondarily. Though Krause, Schloffer, Cushing, Hirsch and others early in the 20th century had introduced pituitary surgery, it was not until 1933 that the first patient with Cushing's disease had neurosurgery performed. This therapy did not gain wide acceptance until Gidot & Thibaut and Hardy pioneered transsphenoidal surgery. Adrenal surgery was for many years the treatment of hypercorticism but prior to the availability of glucocorticosteroids substitution an extremely perilous undertaking.

Adrenal Glands↗
PubMed2000

Detection of viable Chlamydia pneumoniae in abdominal aortic aneurysms.

OBJECTIVES: to investigate the presence of Chlamydia pneumoniae in the wall of abdominal aortic aneurysms (AAAs) and in the aortas of patients without a history of cardiovascular disease. DESIGN: case-control study. MATERIALS: twenty-six consecutive patients operated for AAA were compared to 17 controls. METHODS: aorta was obtained at surgery or autopsy (controls) and prepared for immunohistochemical (IHC) analysis and culture for C. pneumoniae. Throat swabs from 14/26 patients were analysed by PCR for C. pneumoniae. Blood was obtained from 24/26 patients and from 178 70-year-old males. RESULTS: C. pneumoniae was detected in the aortic aneurysms of 20/26 patients by IHC. C. pneumoniae was cultured from 10 of the 20 IHC-positive patients. Only 1/17 controls was positive for C. pneumoniae by IHC (p=0.0001). PCR was positive for C. pneumoniae in 5/14 patients. Serological analysis by microimmunofluoresence (MIF) showed significantly more high titres of the specific antibodies to C. pneumoniae in patients than in age-matched male controls. CONCLUSIONS: we conclude that C. pneumoniae is often present in AAAs in a viable form and that C. pneumoniae is linked to the pathogenesis of AAA.

Aged↗
PubMed1999

Predictive value of malignancy grading systems, DNA content, p53, and angiogenesis for stage I tongue carcinomas.

AIM: To assess the clinical value of malignancy grading systems compared with nuclear DNA content, protein p53, and angiogenesis for predicting recurrence of stage I (UICC, 1987) tongue carcinomas. METHODS: Histopathological malignancy grading according to Jakobsson and tumour front grading according to Bryne et al were performed on haematoxylin and eosin slides. DNA analysis was performed by image cytometry. Protein p53 and angiogenesis were evaluated by immunohistochemical analysis using antibody CM1 and antibody against factor VIII related antigen, respectively. RESULTS: 49 patients with stage I carcinomas of the mobile tongue were included, all treated by local surgical excision alone. Eight patients (16%) suffered from local recurrence during follow up, and 13 (27%) had regional recurrence. Both Jakobsson's malignancy grading system and p53 immunoreactivity proved to be useful predictors of regional recurrence in a Cox multivariate regression analysis. CONCLUSIONS: Histopathological malignancy grading systems provide valuable prognostic information and can still compete with current biological markers in this respect.

Adult↗
PubMed1998

Stereological estimates of nuclear volume in thin malignant melanomas.

Stereological estimation of nuclear volume was performed in a case control study of 72 malignant melanomas, thickness < or = 0.8 mm and Clark's level II-III. However, stereological measurements could be performed in only 57 thin melanomas due to too sparse cellularity. Thus, 21 thin metastasizing melanomas were individually compared with 33 thin non-metastasizing melanomas after individual matching of cases with one or two randomly chosen controls for site of primary tumour, tumour thickness, level of invasion, tumour regression and follow-up. Conditional logistic regression analysis showed no significant differences in nuclear volume between metastasizing and non-metastasizing thin malignant melanomas.

Cell Nucleus↗
PubMed1998

Nuclear DNA content and p53 overexpression in stage I squamous cell carcinoma of the tongue compared with advanced tongue carcinomas.

AIMS: To evaluate the predictive value of the nuclear DNA content (image cytometry) and p53 overexpression (immuno-histochemistry using antibody CM-1) in uniformly treated stage I carcinomas of the mobile tongue. Also, to compare stage I carcinomas with advanced tongue carcinomas (stages II-IV). METHODS: Archival formalin fixed, paraffin wax embedded tumour specimens from 54 patients with stage I squamous cell carcinoma and 37 patients with advanced squamous cell carcinoma were analysed. Mean follow up time of the stage I carcinomas was 71 months (median, 62.5; range, 6-175). RESULTS: Twenty three patients (stage I) had recurring disease: 10 had local recurrence (in the tongue) and 13 had regional recurrence (cervical metastases). Locally recurring stage I carcinomas had a more pronounced DNA deviation than the other stage I carcinomas and this degree of deviation was comparable with the DNA content of advanced carcinomas. Stage I carcinomas that developed regional recurrences overexpressed p53 more frequently. In Cox multivariate regression analysis of time to recurrence, DNA deviation was a significant parameter in tumours that recurred locally (p = 0.032). p53 overexpression was the only parameter close to significance for regional recurrence (p = 0.065). CONCLUSIONS: Nuclear DNA content and p53 immunostaining are of value for the prediction of recurrence of stage I squamous cell carcinomas of the mobile tongue. Stage I tongue carcinomas that are prone to local recurrence show the same DNA content as do advanced tongue carcinomas.

Adult↗
PubMed1998

Stromelysin-3 mRNA expression in dysplasias and invasive epithelial cancer of the larynx.

Matrix metalloproteinases are believed to play an important role in tumor progression, invasion and metastasis. In order to investigate if the expression of stromelysin-3 (ST3) mRNA could add prognostic information concerning invasive laryngeal cancer and/or be indicative of a high risk for tumor progression in laryngeal dysplasias ST3 expression was analyzed by in situ hybridisation of formalin fixed paraffin embedded laryngeal specimens. Furthermore, all specimens underwent image cytometry (ICM) DNA analysis, and, p53 immunostaining. Invasive epithelial cancer, both localized (T1, T2) cancers, cured, as well as not cured, by radiotherapy, and cases with regional lymph node metastases were studied. Furthermore, high grade and low grade dysplasias, selected for rapid, slow and non-progression, as well as non-neoplastic inflammatory lesions were investigated. Expression of the ST3 gene was found in 9 out of 14 (64%) invasive cancer lesions, and in 3 out of 10 (30%) dysplasias, thus indicating that ST3 expression correlates to tumor progression. The ST3 positive laryngeal cancer lesions displayed a higher degree of DNA aberration than the ST3 negative lesions thus suggesting that ST3 positivity could indicate highly malignant tumors. Of the three ST3 positive dysplasias, the first progressed rapidly to cancer in situ with suspected microinvasion. The second ST3 positive dysplasia progressed to invasive cancer within five months. The third ST3 positive dysplasia had been radically excised and hereby cured. All but one of the dysplastic lesions showed p53 immunoreactivity, and all dysplasias exhibited aneuploid cells. ST3 expression appears to be a late event in the multistage process of carcinogenesis and could prove useful as an indicator of dysplasias with imminent risk for progression to invasive cancer.

Humans↗
PubMed1998

Reproducibility and efficiency testing of two sampling methods for image analysis in cytology.

OBJECTIVE: Quantitative nuclear DNA analyses and nuclear morphometry have become a widely used tool in pathology. Nevertheless, studies done by different observers utilizing the same methods very often have shown different results. One of the reasons could be that different sampling methods were used. In this study two selection methods for image analyses (the consecutive selection method and the random selection method) were tested for reproducibility and efficiency. STUDY DESIGN: Using an interactive imaging analysis system, 10 cases (5 breast adenocarcinomas, 3 prostatic cancers, 1 sarcoma, 2 prostatic hyperplasias) were measured twice by using each sampling method. Median nuclear area and entropy (i.e., a statistical descriptor of DNA histograms) were the parameters calculated. RESULTS: The results showed that using the consecutive selection method, the number of individual nuclei in a cytologic sample that should be measured to obtain reproducible results was 150 for nuclear area and 110 for entropy. The corresponding figures using random systematic selection method were 80 for assessment of nuclear area and 100 for assessment of entropy. CONCLUSION: Both methods showed high reproducibility and a good correlation with each other. The mathematical idea of "plateau values," which was used to estimate the number of measurements needed, was considered a good contribution to increasing the efficiency of both methods.

Breast Neoplasms↗
PubMed1997

p53 immunostaining and image cytometry DNA analysis in precancerous and cancerous squamous epithelial lesions of the larynx.

BACKGROUND: Squamous epithelial cancer can develop from progressive epithelial changes connoted dysplasias. Histopathologic evaluation/grading of these lesions is difficult and gives poor information concerning the risk for progression to cancer. Squamous cell carcinoma of the head and neck (SCCHN) frequently show p53 alteration and DNA-ploidy aberration. Could these markers be used as indicators for malignancy risk in the larynx? METHODS: Immunohistochemical staining (IHC), with the CM-1 antibody against p53, and image cytometry (ICM) DNA analysis were performed in 60 lesions from 12 patients--and 21 controls--who were initially seen with laryngeal lesions prior to cancer in situ (cis) or invasive cancer diagnosis at the same site. RESULTS: All but one of the invasive cancers, and 77% of the lesions which preceded cancer or cancer in situ, showed positive p53 immunostaining, as compared with only 10% of the controls. All but one of the invasive cancer lesions, and 77% of the precancerous lesions, showed aberrant DNA-ploidy results, whereas all controls were diploid. When DNA and p53 analysis were combined, only one of the lesions preceding cis or invasive cancer was negative. CONCLUSIONS: Both p53 immunoreactivity and DNA-ploidy aberration appear to be early events in the multistep process of squamous epithelial carcinogenesis. Immunohistochemical staining p53 analysis and ICM DNA analysis does increase the diagnostic sensitivity for cancerous and true precancerous lesions in the larynx.

Adult↗
PubMed1997

Analysis of nuclear DNA and morphometry, and proliferating cell nuclear antigen in primary and metastatic malignant melanoma.

Sections from 23 primary malignant melanomas and 39 corresponding metastases were analysed for DNA content, nuclear morphometry, and proliferating cell nuclear antigen (PCNA). In 15 of 23 patients (65%) both primary and secondary tumours showed similar DNA patterns, whereas a disparity was found in the remaining eight patients (35%). The 23 primary tumours and groups of metastases (from different patients) located in skin, lymph nodes, and brain did not differ significantly in any of the variables investigated. Cox stepwise regression analysis indicated that a large variability (CV) of nuclear area in the first metastasis correlated with increased survival after recurrence (p = 0.039) as well as with survival (p = 0.031).

Adult↗