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Biomedical subjects

T Sane

Publications and source records attributed to T Sane.

At least 19 recordsLinked to original sources
PubMed2000

Long term prognosis of medullary thyroid carcinoma in 39 patients.

BACKGROUND AND AIMS: Thyroidectomy and radical cervical lymph node dissection have been suggested as primary and secondary operations aimed at achieving biochemical cure in cases of medullary thyroid carcinoma (MTC). The purpose of this study was to find out behaviour of MTC in long-term follow-up, and to estimate possible difference in biological virulence between sporadic MTC and MTC in MEN2A. MATERIAL AND METHODS: From 1967 through 1994, 39 patients with MTC, including 9 patients with hereditary disease, were operated on at the Second Department of Surgery, Helsinki University Central Hospital. Enlarged lymph nodes were dissected selectively. The main outcome measure was carcinoma-specific survival. RESULTS: In sporadic MTC, ten-year carcinoma-specific survival was 57.9% (95% CI 39.1%-76.7%) and ten-year survival after reoperation due to lymphatic node recurrence was 51.4% (CI 18.7%-84.2%). The presence of distant metastases at diagnosis (p = 0.0001) and extrathyroidal growth of the primary tumor (p = 0.0008) were independent predictors of carcinoma-specific survival in the Cox model. The risk ratio of sporadic MTC to MTC in MEN2A was 5.40 (CI 0.67-43.2) after adjusting the survival time for the size of the primary tumor. CONCLUSION: Distant metastases and the local extrathyroidal extent of the primary tumor have a significant effect on the prognosis of MTC, lymphatic node metastases and other clinical factors being less important. The biological virulence of sporadic MTC may be clinically significantly higher than that of MTC in MEN2A.

Adult↗
PubMed1999

The survival and well-being of patients treated for Cushing's syndrome.

OBJECTIVE: The main aim of the study was to evaluate the survival, well-being and working capacity of patients treated for Cushing's syndrome. DESIGN: The study was carried out by retrospectively analysing patient records from years 1981-94. Follow-up time was extended from the time of diagnosis to the end of 1996. A questionnaire dealing with symptoms prior to and after therapy, and the quality of life estimated on a Visual Analogue Scale (VAS) was sent to all surviving patients. SETTING: The study was performed in a university hospital. MAIN OUTCOME MEASURES: Survival, subjective well-being, working capacity before and after treatment and disappearance of symptoms after treatment of Cushing's syndrome. RESULTS: During the follow-up time 10 patients died out of a total of 74. The overall standardized mortality ratio (SMR) was 168% (95% CI 81-309%). The SMR of patients with pituitary disease was 267% (89-525%), and in patients with adrenal adenoma it was 135% (16-489%). Forty-six per cent of the surviving patients stated that they felt fully recovered from the disease, but the proportion of patients having persisting symptoms after treatment was also noteworthy. The mean VAS score (range 0-100) was 19 (SD 14) before treatment and 82 (SD 18) after treatment (P<0.001). After treatment, 81% of the patients were able to return to work, 11% retired because of disability, 5% retired because of age and 3% were on sick-leave at the time of answering the questionnaire. During the follow-up time, 42% of the patients with pituitary disease suffered a relapse. However, the effect of the relapse on well-being was not significant. CONCLUSIONS: The mortality risk of patients treated for Cushing's disease was not significantly increased compared with that of the general population. Many symptoms persisted even years after therapy. After clinical recovery, working ability was not always regained.

Adolescent↗
PubMed1999

Ovarian hyperstimulation caused by gonadotroph adenoma secreting follicle-stimulating hormone in 28-year-old woman.

Ovarian hyperstimulation caused by a gonadotroph adenoma in premenopausal women has been described only twice before this report. A 28-yr-old woman presented with menstrual disturbances and pelvic pains that began after stopping the use of contraceptive pills. Transvaginal ultrasound revealed enlarged ovaries with multiple cysts. The patient had elevated serum estradiol (up to 2900 pmol/L; normal, 80-300 pmol/L in the follicular phase) and inhibin (6.4 kU/L; normal, 0.5-2.5 kU/L) levels. Serum LH was appropriately suppressed (0.6 IU/L), but serum FSH varied from 4.9-8.1 IU/L. Both gonadotropins as well as the free alpha-subunit showed a paradoxical response to the stimulus by TRH. A nuclear magnetic resonance study unraveled a pituitary tumor, 12-14 mm in diameter, extending up to the suprasellar cistern. After pituitary surgery, all hormone values normalized, and the patient resumed regular ovulatory cycles. In immunostaining, 20-30% of the cells of the tumor stained positively for FSHbeta. We conclude that a gonadotropin-producing adenoma must be considered in the differential diagnosis of a patient presenting with large multicystic ovaries and high estradiol levels in the absence of exogenous gonadotropins.

Adenoma↗
PubMed1998

Risk factors for mortality in Type II (non-insulin-dependent) diabetes: evidence of a role for neuropathy and a protective effect of HLA-DR4.

To test the hypothesis that interaction between genetic, immunological, clinical and metabolic risk factors influences the outcome of Type II (non-insulin-dependent) diabetes mellitus, we examined which of the above factors present at baseline were associated with mortality in 134 Type II diabetic patients followed for 9 years. Thirty-eight patients (29%) died during the follow-up period; the majority of whom (68%) died from cardiovascular disease. At baseline, the deceased patients had higher HbA1c values (p = 0.002), higher LDL-triglycerides (p = 0.007), lower HDL-cholesterol (p = 0.007), higher non-esterified fatty acid (NEFA) concentrations (p = 0.014), and higher albumin excretion rate (p < 0.0001) than the patients who survived. In addition, the frequency of HLA-DR4 (21 vs 39%, p = 0.048) and of parietal cell antibodies (5 vs 14%, p = 0.016) were decreased in the deceased as compared to the living patients. Patients who died during follow-up also had more retinopathy (42 vs 16%, p = 0.002), neuropathy (57 vs 23%, p < 0.001), microalbuminuria (45 vs 6%, p < 0.0001), coronary heart disease (50 vs 13%, p < 0.0001), and peripheral vascular disease (27 vs 9%, p = 0.005) at baseline than patients who survived. In a multiple logistic regression analysis macroangiopathy (p = 0.004), neuropathy (p = 0.007), HbA1c (p = 0.018) and albumin excretion rate (p = 0.016) were independent risk factors for death. In patients free of cardiovascular disease at baseline, conventional risk factors such as LDL-cholesterol (p = 0.005) and age (p = 0.003) were associated with subsequent development of cardiovascular disease. In conclusion, in addition to coexisting macroangiopathy, increased albumin excretion rate, poor glycaemic control and neuropathy are risk factors for cardiovascular mortality in patients with Type II diabetes. The presence of HLA-DR4 and signs of autoimmunity may be associated with decreased risk of cardiovascular disease.

Adult↗
PubMed1998

Predictors of progression from normoalbuminuria to microalbuminuria in NIDDM.

OBJECTIVE: Our objective was to establish the clinical, genetic, metabolic, and immunologic risk factors for the progression of the albumin excretion rate (AER) in normoalbuminuric NIDDM patients. RESEARCH DESIGN AND METHODS: We recruited 108 NIDDM patients with normal AER after a diabetes duration of 9 years to participate in a prospective 9-year follow-up. In addition to conventional clinical and metabolic variables, we assessed microvascular (retinopathy, nephropathy, neuropathy) and macrovascular (coronary heart disease, peripheral vascular disease) diabetic complications, genetic markers (HLA genotypes), and organ-specific autoimmune markers, including islet cell antibodies. Multiple logistic regression was used to determine independent predictors of progression of AER. RESULTS: A total of 21 patients (19%) died during the follow-up. There was an overrepresentation of men (61 vs. 39%; P = 0.044) and smokers (55 vs. 27%; P = 0.01) in patients who progressed to micro- or macroalbuminuria versus those who did not progress. In addition, progressors had higher fasting plasma glucose (P = 0.002) and HbA1 (P = 0.0002) concentrations at baseline than did nonprogressors. Neuropathy was more often seen in progressors than in nonprogressors at baseline (53 vs. 16%; P = 0.0004). Frequency of HLA genotypes and autoimmune markers did not differ between progressors and nonprogressors. In a multiple logistic regression analysis, HbA1 (P = 0.0005) and a history of smoking (P = 0.011) were independent predictors of progression of AER. CONCLUSIONS: This study reemphasizes the importance of poor glycemic control and smoking as independent risk factors for progression of AER. Furthermore, development of micro- or macroalbuminuria in NIDDM was associated with neuropathy and male sex.

Adult↗
PubMed1996

Long-term effects of pregnancy on diabetic complications.

The aim of our study was to establish whether pregnancy affects long-term development and progression of retinopathy and nephropathy in diabetic women compared to nulliparous diabetic women. Twenty-eight diabetic women who had delivered in 1983-85 at Helsinki University Central Hospital and 17 nulliparous controls matched according in age, duration of diabetes, and degree of vascular complications were personally interviewed and the current retinal status and renal function were assessed 7 years later, in 1990-92. Serum creatinine, creatinine clearance, nocturnal albuminuria, and HbA1c were measured and colour fundus photography carried out. The results were compared to the status in 1983-85. Of those who had been pregnant, 5 of 26 (19.2%) had experienced worsening of retinopathy. In 3 of these, proliferative retinopathy had developed from only minimal background changes. In the control group, progression had occurred in 8 cases of 16 (50%, p < 0.05). The groups did not differ from each other regarding progression or development of nephropathy. This suggests that pregnancy does not seem to affect development or progression of diabetic nephropathy whereas progression of retinopathy seems to occur less often after pregnancy compared to nulliparous women.

Adult↗
PubMed1996

Interstitial radiotherapy of 25 parasellar/clival meningiomas and 19 meningiomas in the elderly. Analysis of short-term tolerance and responses.

I-125 seeds were permanently implanted into 25 parasellar-clival meningiomas (median age of patients, 56 y) and 19 globoid meningiomas in the elderly (median age of patients, 77 y) using stereotactic technique and 3-D dose planning. Total dose at the tumour margin was increased during the series from 100 Gy to 150 Gy. The procedure caused no mortality and no serious bleeding, but injury to the III cranial nerve due to puncture occurred in one (4%) of the 25 parasellar-clival meningiomas. In two (4.5%) of the 44 cases the postoperative CT scan showed a misplaced seed, located at the tumour surface. Nonenhancing hypodense rings developed around the seeds ('hot spots') with a median diameter of 10.5 mm at 12 months corresponding to a median initial activity of 8.7 mCi. In general, meningiomas responded by slow reduction in volume. The parasellar-clival meningiomas were followed-up for a median of 19 months (6-32), and so far 4 tumours have shrunk moderately, 13 slightly, and 5 not at all. Pre-operative III, V or VI cranial nerve signs were present in 17 patients and subsided in 8 of them. On the other hand, facial numbness developed or increased in 9 of the 25 patients, indicating that the V nerve is rather sensitive to this type of irradiation. In the 19 meningiomas of the elderly, the median follow-up time was 14 months (5-26). The median relative tumour volume was 46% at 12 months. Accounting for tumour-related deaths only, the actuarial survival rate was 78% at 12 months and 62% at 24 months. In general, brain oedema persisted despite reduction in tumour volume. Stereotactic implantation of I-125 seeds into intracranial meningiomas is relatively safe. Interstitial radiotherapy represents a potential tool in the control of medium-sized intracranial meningiomas with minimal brain oedema, but its long-term impact and untoward effects remain to be followed-up.

Adult↗
PubMed1996

Postmarathon paradox: insulin resistance in the face of glycogen depletion.

Acute physical exercise enhances insulin sensitivity in healthy subjects. We examined the effect of a 42-km marathon run on insulin sensitivity and lipid oxidation in 19 male runners. In the morning after the marathon run, basal serum free fatty acid concentration was 2.2-fold higher, muscle glycogen content 37% lower (P < 0.01), glycogen synthase fractional activity 56% greater (P < 0.01), and glucose oxidation reduced by 43% (P < 0.01), whereas lipid oxidation was increased by 55% (P < 0.02) compared with the control study. During euglycemic-hyperinsulinemic clamp, whole body glucose disposal was decreased by 12% (P < 0.01) because of a 36% lower glucose oxidation rate (P < 0.05), whereas the rate of lipid oxidation was 10-fold greater (P < 0.02) than in the control study. After the marathon, muscle glycogen content correlated positively with lipid oxidation (r = 0.60, P < 0.05) and maximal aerobic power (Vo2peak; r = 0.61, P < 0.05). Vo2peak correlated positively with basal lipid oxidation (r = 0.57, P < 0.05). In conclusion, 1) after the marathon run, probably because of increased lipid oxidation, the insulin-stimulated glucose disposal is decreased despite muscle glycogen depletion and the activation of glycogen synthase; 2) the contribution of lipid oxidation in energy expenditure is increased in proportion to physical fitness; 3) these adaptations of fuel homeostasis may contribute to the maintenance of physical performance after prolonged exercise.

Adult↗
PubMed1995

LDL particle size in mildly hypertriglyceridemic subjects: no relation to insulin resistance or diabetes.

We examined 18 Type 2 diabetic and 19 non-diabetic subjects in order to determine the association between insulin resistance and LDL particle size distribution in mildly hypertriglyceridemic and hyperinsulinemic subjects with and without Type 2 diabetes. Insulin sensitivity of the patients was characterized by their insulin-stimulated glucose uptake rate determined by euglycemic clamp technique. LDL particle size distribution was determined by nondenaturing polyacrylamide gradient gel electrophoresis. Type 2 diabetic and non-diabetic subjects had closely similar serum lipid and lipoprotein concentrations as well as the mean particle diameters of the major LDL peak (246 +/- 6 A and 244 +/- 6 A, respectively). To evaluate the effect of insulin resistance on LDL particle size the participants were categorized into two subgroups using the median of their insulin-stimulated glucose uptake rate (14.67 mumol/kg/min) as a cut-off point. Neither lipid and lipoprotein concentrations nor the LDL particle size distributions differed between the more insulin resistant group (nine diabetic and nine non-diabetic subjects) and less insulin resistant group (nine diabetic and ten non-diabetic subjects). LDL particle size was not associated with the insulin-stimulated glucose uptake rate or with the mean 24-h concentration of serum insulin. Mean 24-h concentration of serum triglycerides was the strongest discriminator for LDL particle size (r = -0.44, P < 0.01). In conclusion, neither Type 2 diabetes nor insulin resistance seem to have any direct effect on LDL particle size in mildly hypertriglyceridemic subjects. The fact that LDL particle size was associated with serum triglycerides indicates that the effect of diabetes and insulin resistance on LDL particle size could be explained by the effects of insulin resistance and/or hyperinsulinism on VLDL metabolism.

Blood Glucose↗
PubMed1995

Decreasing triglyceride by gemfibrozil therapy does not affect the glucoregulatory or antilipolytic effect of insulin in nondiabetic subjects with mild hypertriglyceridemia.

We studied the effects of gemfibrozil on glucose and fatty acid metabolism in subjects with mild endogenous hypertriglyceridemia. Twenty subjects (serum triglycerides, 3.2 +/- 1.4 mmol/L; age, 52 +/- 7 years; body mass index, 27.8 +/- 1.8 kg/m2) were randomly allocated to receive either placebo or gemfibrozil 1,200 mg daily for 12 weeks in a double-blind study. Gemfibrozil decreased serum total and very-low-density lipoprotein (VLDL) triglycerides by 53% and 57%, respectively, and serum apolipoprotein (apo) B concentration by 21%. Gemfibrozil had no effect on the diurnal concentration of free fatty acids (FFA). Neither did gemfibrozil change diurnal blood glucose or serum insulin concentrations. The endogenous glucose production rate remained unchanged in both groups during the treatment period, and was similarly suppressed by hyperinsulinemia. The rate of insulin-induced whole-body glucose disposal increased similarly both before (basal 10.8 +/- 1.8, low-dose insulin 10.5 +/- 2.1, and high-dose insulin 20.9 +/- 11.9 mumol.kg-1.min-1) and after (11.1 +/- 1.7, 10.7 +/- 1.2, and 18.6 +/- 7.9, respectively) gemfibrozil treatment. Rates of oxidative and nonoxidative glucose metabolism remained unchanged during gemfibrozil treatment. Basal pretreatment and posttreatment FFA turnover rates were similar in both study groups, as were the rates of substrate oxidation. In summary, gemfibrozil proved to be an effective serum triglyceride-lowering agent in patients with mild hypertriglyceridemia, but had no effect on the insulin sensitivity of glucose metabolism or of antilipolysis. These data support the idea that triglycerides per se do not cause insulin resistance, and that the triglyceride-lowering effect of gemfibrozil is not mediated via antilipolytic action.

Analysis of Variance↗
PubMed1995

Effect of gemfibrozil on the regulation of HDL subfractions in hypertriglyceridaemic patients.

OBJECTIVES: To study changes of HDL subfractions and their regulation during gemfibrozil treatment in hypertriglyceridaemia. DESIGN: Twenty patients with hypertriglyceridaemia were randomized to receive either 1200 mg day-1 gemfibrozil or placebo for 3 months. After a 6-week, single-blind placebo period, the patients were randomized to receive either gemfibrozil or placebo for 3 months in a double-blind study. SETTING: The patients were studied as outpatients in the Third Department of Medicine, Helsinki University Central Hospital, Helsinki, Finland. MAIN OUTCOME MEASURES: Ultracentrifugally isolated HDL subclasses; concentrations of apoA-I, apoA-II, LpA-I and LpA-I:A-II particles; post-heparin plasma lipoprotein lipase (LPL), hepatic lipase (HL) and plasma cholesteryl ester transfer protein (CETP) activities; phospholipid transfer protein (PLTP) and lecithine cholesteryl acyltransferase (LCAT) activities were measured in plasma from six patients from both groups. RESULTS: Gemfibrozil increased the concentration of HDL cholesterol (+11.1%) because of the rise of HDL3 cholesterol (34.5%, P < 0.01). The concentration of LpA-I particles was reduced during gemfibrozil treatment (-12.4%, P < 0.05), while that of apoA-II increased (+12.3%, P < 0.01). The LpA-I to LpA-I:A-II ratio decreased significantly in the gemfibrozil group (-18.9%, P < 0.01). Gemfibrozil increased LPL and HL activities by 18.2% (P < 0.05) and by 19.6%, respectively. Plasma CETP activity was also increased during gemfibrozil treatment (+15.8%, P < 0.05). CONCLUSION: The gemfibrozil-induced elevation of HDL3 and apoA-II may reflect the combined action of LPL, HL and CETP on plasma HDL metabolism.

Adult↗
PubMed1994

No evidence for linkage between familial hypertriglyceridemia and apolipoprotein B, apolipoprotein C-III or lipoprotein lipase genes.

Familial hypertriglyceridemia has been suggested to be an autosomal dominant condition with age-dependent penetrance, but so far the underlying defective gene has not been elucidated. We examined the possible role of three candidate gene loci by linkage analysis in six Finnish families with familial clustering of hypertriglyceridemia. The probands were initially recruited from a group of hyperlipidemic outpatients after measurement of serum triglyceride concentrations exceeding 2.00 mmol/l on two occasions. Altogether, 71 subjects were included in the linkage analyses. Bi- or multiallelic DNA polymorphisms were used as markers for the apolipoprotein B gene (chromosome 2), lipoprotein lipase gene (chromosome 8), and apolipoprotein A-I/C-III/A-IV gene cluster (chromosome 11). Linkage analysis was performed by applying two alternative phenotyping models, one adopting quantitative serum triglyceride concentrations and another using qualitative classification of the subjects into hypertriglyceridemic, normotriglyceridemic, and borderline hypertriglyceridemic groups. Using either approach, the cumulative lod scores of each of the three candidate genes in the six families were less than -2.0 at the recombination fraction 0.0. These results suggest that none of the candidate genes investigated is involved in familial clustering of hypertriglyceridemia in our study.

Adult↗
PubMed1994

Hyponatremia after transsphenoidal surgery for pituitary tumors.

We studied the incidence of postoperative hyponatremia in 91 consecutive patients (44 males and 47 females; age, 45 yr; range, 12-76) operated on transsphenoidally for pituitary tumors. A postoperative serum sodium concentration less than 135 mmol/L (the lowest, 109 mmol/L) was observed in 32 (35%) patients. Hyponatremia occurred most commonly in patients operated on for Cushing's disease (11 of 18 patients; 61%). Hyponatremia was symptomatic in 18 (56%) of the patients. Neither the size nor the operability of the tumor or transient postoperative polyuria predicted the development of hyponatremia. Hyponatremia was first observed on the sixth or seventh postoperative day. The patients were treated with water restriction and by increasing the hydrocortisone replacement dose in the case of ACTH deficiency, and recovery took place, on the average, within 5 days. High urinary osmolality and plasma arginine vasopressin concentration during hyponatremia in a subgroup of study patients with these measurements indicated that inappropriate vasopressin secretion was involved in the pathogenesis of hyponatremia. In conclusion, postoperative hyponatremia after transsphenoidal surgery is common and may put the patients at increased risk of severe hyponatremic symptoms. Therefore, all patients should be screened for serum electrolytes for 1 week after transsphenoidal surgery.

Adenoma↗
PubMed1993

Does familial hypertriglyceridemia predispose to NIDDM?

OBJECTIVE: To determine the 10-yr incidence of impaired glucose tolerance and NIDDM in families with a clustering of endogenous hypertriglyceridemia. RESEARCH DESIGN AND METHODS: The prospective population study, where the oral glucose tolerance test and the measurement of serum lipids and lipoproteins were performed at the baseline examination and after the 10-yr follow-up, was conducted on 56 subjects (17-60 yr of age at the baseline). The subjects were from six pedigrees with a clustering of endogenous hypertriglyceridemia, and 47 of these subjects attended the follow-up 10 yr later. RESULTS: In the study families, the prevalence of glucose intolerance and NIDDM increased from 15 to 49% (P < 0.001) and from 2 to 21% (P < 0.001), respectively, over the 10-yr period. When grouped according to the baseline serum triglyceride tertiles, 76% (P < 0.01) of the family members with highest serum triglycerides were glucose intolerant (29% impaired glucose tolerance, 47% NIDDM) at follow-up compared with 20% of those with lowest serum triglycerides. In discriminant analysis, including age, body mass index, treatment with thiazides and beta-blocking agents, and 2-h serum insulin concentration, the baseline serum triglycerides still remained as an independent predictor of development of impaired glucose tolerance and NIDDM. CONCLUSIONS: Families with a clustering of hypertriglyceridemia are at increased risk of NIDDM, and in these families elevation of serum triglycerides serves as a risk marker of glucose intolerance and NIDDM.

Adult↗