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Biomedical subjects

H Mäkisalo

Publications and source records attributed to H Mäkisalo.

At least 19 recordsLinked to original sources

Toxic acute hepatitis and hepatic fibrosis after consumption of chaparral tablets.

In this report we describe a young, previously healthy woman who developed severe acute hepatitis after consumption of chaparral tablets, a commonly used herbal product. In this case, the elimination-rechallenge event and the exclusion of other possible aetiologic factors strongly supported true causality between the herbal product and the liver damage. Primary liver biopsy showed severe toxic hepatitis consistent with previous reports of chaparral-induced liver damage. Later, 6 months after the liver function tests had normalized, permanent hepatic fibrosis could still be seen.

Adult↗

Outcome following liver transplantation for primary sclerosing cholangitis in the Nordic countries.

BACKGROUND: Primary sclerosing cholangitis (PSC) is the most common indication for liver transplantation in the Nordic countries. Because these patients are difficult to evaluate with regard to timing of liver transplantation, it is important to establish predictors of post-transplant survival. METHODS: Data from two groups of patients receiving liver allografts during 1982-2001 were recorded: (a) PSC patients and (b) comparison patients. Outcome following transplantation has been recorded for all patients. Regression analyses have been performed for PSC patients to analyse predictors of patient and graft survival. RESULTS: A total of 245 PSC and 618 comparison patients received a first liver allograft in the period 1982 until the end of the study. The overall 1-, 3- and 5-year patient survival rates were 82%, 77% and 75%, and 80%, 77% and 74% in the PSC group and comparison group, respectively. Survival following transplantation has increased with time in both the PSC and the comparison group. Recent year of transplantation, no previous hepatobiliary surgery and a lower MELD score were predictors of survival following transplantation for PSC patients. PSC patients had a higher rate of re-transplantations (13% versus 8%, P = 0.01). Predictors of re-transplantation in PSC patients were an episode of early rejection and vascular thrombosis. CONCLUSION: In PSC patients, year of transplantation, previous hepatobiliary surgery and MELD score are predictors of survival following transplantation and these patients are more frequently in need of re-transplantation compared to the comparison group.

Adolescent↗

Transhepatic neutrophil and monocyte activation during clinical liver transplantation.

BACKGROUND: During experimental liver transplantation, neutrophil sequestration results in increased oxygen free radical production and correlates inversely with graft viability. Neutrophil activation in clinical liver transplantation is poorly understood. METHODS: We assessed leukocyte sequestration and transhepatic differences of neutrophil and monocyte CD11b expression, neutrophil free radical production, and plasma concentrations of interleukin 6 and interleukin 8 in nine patients during liver transplantation. RESULTS: Significant hepatic neutrophil sequestration occurred during initial graft rewarming with portal blood, after inferior vena cava declamping, and after hepatic artery declamping (all P<0.05). A positive transhepatic difference (i.e., outcoming - ingoing) in CD11b expression of neutrophils was observed after portal vein declamping (51+/-32 relative fluorescence unit [RFU]) and in CD11b expression of monocytes during initial graft rewarming (67+/-86 RFU, both P<0.05). A transcoronary increase in both unstimulated (74+/-80 RFU) and N-formyl-methionyl-leucylphenylalanine-stimulated (112+/-168 RFU) neutrophil free radical production took place after hepatic artery declamping (both P<0.05). A negative transcoronary difference of interleukin 6 occurred during initial graft rewarming (-192+/-176 pg/ml) and a positive difference of interleukin 8 occurred after hepatic artery declamping (17+/-23 pg/ml, both P<0.05). CONCLUSIONS: Hepatic sequestration and transhepatic activation of neutrophils, and hepatic production of interleukin 8 occur during clinical liver transplantation. A splanchnic influx of interleukin 6 occurs to the graft, possibly modulating neutrophil-mediated graft reperfusion injury.

Adult↗

Liver transplantation in patients over 60 years of age.

Liver transplantation was previously only offered to patients under 60 years of age. We have analyzed the outcome after acceptance on the waiting list and after liver transplantation of patients over 60 years old. A total of 150 patients over 60 years old were listed for a first liver transplantation during 1990-1998. The annual number increased throughout the period. Primary biliary cirrhosis, primary sclerosing cholangitis, and acute hepatic failure were the most frequent diagnoses. A total of 119 patients received a first liver allograft. The patient 1-year survival was 75% and 3-year survival 62%, which was not significantly lower (P = 0.21) than that of the younger patients. When correcting for year of transplantation, the survival was, however, moderately but significantly lower than among the younger patients. Survival among those > 65 years (n = 38) did not differ from that of patients 60-65 years of age (n = 81). We conclude that an increasing number of patients over 60 years old can be listed for liver transplantation and receive a liver allograft with highly satisfying results.

Age Distribution↗

Are diabetic patients in danger at renal transplantation? An invasive perioperative study.

It is assumed that diabetic patients with uraemia have more complications at renal transplantation than those who are not diabetic. We compared the preoperative ECGs, and invasive perioperative haemodynamic and oxygenation parameters in 15 diabetic and 15 non-diabetic uraemic patients undergoing renal transplantation. The number of patients with increased QT dispersion in the ECG was higher in diabetic than in non-diabetic patients (P<0.05). Before anaesthesia, heart rate and mean arterial pressure were higher (P<0.05) in the diabetic than in the non-diabetic group. After preanaesthetic volume loading all patients showed a hyperdynamic circulation, which subsided during anaesthesia. However, stroke volume index remained unchanged. Four patients in the diabetic group and six in the non-diabetic group needed additional oxygen therapy after surgery. No cardiac dysrhythmias were noted. However, the increased QT dispersion in diabetic patients calls for an adequate perioperative ECG monitoring for dysrhythmias. The diabetic and non-diabetic uraemic patients performed equally well at renal transplantation. In conclusion, renal transplantation for diabetics is justified.

Adult↗

Acute effect of alcohol on androgens in premenopausal women.

The aim of the present study was to investigate the effect of alcohol on androgen levels among premenopausal women. Eighty-seven women in the mid-cycle phase of the menstrual cycle, 47 of whom used oral contraceptives (OC+), were included in the study. The range for reported alcohol consumption was 0-4 drinks/day. The total testosterone levels were significantly higher after alcohol intake (0.5 g/kg) than after placebo at 45 min and 90 min from the start of drinking among both OC- and OC+ subjects. This effect was also seen in the free testosterone fraction. The effect on testosterone was more prominent among OC+ subjects. Androstenedione levels were significantly lowered and the testosterone:androstenedione ratio significantly elevated by alcohol among both OC- and OC+ subjects. No effect of alcohol on dehydroepiandrosterone or dihydrotestosterone levels was observed. A positive correlation was observed between the change in testosterone levels and the change in androstenedione levels during placebo conditions. The correlation was significantly reduced during alcohol conditions among OC+ subjects, indicating an increased androstenedione to testosterone conversion. No significant dose (0.34, 0.68 and 1.02 g/kg) or time (45, 90 and 150 min) effects on total testosterone were observed in a substudy involving 10 OC+ subjects. The present results suggest that the testosterone effect is related to the zero-order mechanism of ethanol oxidation. The observed testosterone and androstenedione effects are suggested to be the result of an increased androstenedione to testosterone conversion in the liver caused by the alcohol-mediated elevation in the [NADH]:[NAD(+)] ratio. The present findings may be relevant in the development of hyperandrogenism and loss of female sexual characteristics associated with heavy alcohol consumption.

Adult↗

Carbohydrate 19-9 antigen as a marker of non-malignant hepatocytic ductular transformation in patients with acute liver failure. A comparison with alpha-fetoprotein and carcinoembryonic antigen.

BACKGROUND: We have observed increased serum tumor markers, especially carbohydrate antigen 19-9 (CA 19-9) levels, in patients with acute liver failure (ALF) being evaluated for liver transplantation, raising the question of potential malignancy. In chronic liver disease increased serum alpha-fetoprotein (AFP) may be a sign of liver regeneration, but little is known of these markers in ALF. The aim of this study was to evaluate the causes of overexpression of tumor markers in patients with non-malignant ALF. METHODS: The serum AFP, carcinoembryonic antigen (CEA), and CA 19-9 levels were compared with the liver function tests in 33 patients with acute liver failure and in 78 patients with chronic non-malignant liver disease being evaluated for liver transplantation. Immunohistochemical stainings of the tumor markers were performed on explanted liver specimens. RESULTS: The AFP (1-218 U/ml) and CA 19-9 (10-6520 U/ml) levels were significantly higher in the patients with ALF than in the patients with chronic liver disease (P < 0.01). The AFP and CA 19-9 values also correlated with the total serum bilirubin level. In the patients with ALF the immunohistochemical staining for CA 19-9 was highly positive in periportal transformed ductular hepatocytes and correlated positively with the serum CA 19-9 values (P < 0.001). The stainings for AFP or CEA showed no or only slight positivity in the patients with increased serum values of the tumor markers. CONCLUSIONS: In patients with ALF increased serum levels of CA 19-9 reflect the amount of transformed ductular hepatocytes without any evidence of malignancy. Increased CA 19-9 values should not be the cause of delay when an ALF patient needs an urgent liver transplantation.

Biomarkers, Tumor↗

Hepatic and splanchnic oxygenation during liver transplantation.

OBJECTIVE: To evaluate hepatic and splanchnic oxygenation during liver transplantation. DESIGN: Prospective study. SETTING: University hospital. PATIENTS: Ten adult patients undergoing liver transplantation. INTERVENTIONS: Standardized surgery and anesthesia without venovenous bypass. MEASUREMENTS AND MAIN RESULTS: Hepatic oxygenation was assessed by analyzing oxygen tension, oxygen saturation, and lactate concentration in hepatic venous blood. Splanchnic oxygenation was assessed by analyzing oxygen tension, oxygen saturation, and lactate concentration in portal venous blood and by gastric tonometry. Before reperfusion, the grafts were flushed with 1000 mL of acetated Ringer's solution and 400 mL of portal venous blood. The effluent blood from the graft was wasted and showed a mean pH of 6.86 and a lactate concentration of 9.4 mmol/L. Five minutes after portal reperfusion, most of the grafts produced lactate. Portal-hepatic venous P(CO2) difference ranged from 3 to 16 torr (0.4-2.1 kPa). By the time of restoration of the infrahepatic caval flow mean 24 mins later, eight of the grafts had stopped producing lactate. Mean hepatic venous oxygen tension was 47 torr (6.3 kPa), stabilizing to 41 torr (5.5 kPa) at the end of surgery. Acidosis resolved without pharmacologic interventions. Mean gastric mucosal pH was 7.29 during the anhepatic phase and 7.40 at the end of surgery. One of the patients developed hepatic arterial thrombosis intraoperatively. Her data were analyzed separately. Later, the other patients recovered with good liver function, whereas the patient with hepatic arterial thrombosis was successfully retransplanted. CONCLUSIONS: The liver grafts received well-oxygenated portal venous blood during reperfusion, despite the low values of gastric mucosal pH immediately before reperfusion. Hepatic oxygenation became adequate soon after reperfusion. In the patient with hepatic arterial thrombosis, the recovery of hepatic oxygenation was impaired and lactic acidosis persisted.

Adult↗

Acute effect of alcohol on estradiol, estrone, progesterone, prolactin, cortisol, and luteinizing hormone in premenopausal women.

BACKGROUND: Heavy alcohol consumption is associated with menstrual irregularities, including anovulation, luteal-phase dysfunction, recurrent amenorrhea, and early menopause. In addition, moderate to heavy alcohol intake has been found to increase the risk of spontaneous abortions and breast cancer. These adverse effects could at least in part originate from alcohol-mediated changes in hormone levels. METHODS: The acute effect of alcohol on the hormone balance in women using oral contraceptives (OC+) and also in nonusers (OC-), was evaluated in 30 OC- and 31 OC+ subjects, representing the whole period of the menstrual cycle. It was also evaluated in 40 OC- and 47 OC+ subjects during the midcycle phase and in 10 OC+ subjects with unknown cycle phase. RESULTS: We found that among subjects who used oral contraceptives, estradiol levels increased and progesterone levels decreased after intake of alcohol (0.5 g/kg). No dose effect (0.34-1.02 g/kg) on progesterone was observed in a substudy on 10 OC+ subjects. With regard to estrone levels, no effect was observed, although a significant increase was found in the estradiol-to-estrone ratio. Among subjects not using oral contraceptives, progesterone levels decreased after intake of alcohol (0.5 g/kg). No effect was found in estradiol, estrone, or the estradiol-to-estrone ratio during midcycle in this study group. A transient elevating effect of alcohol (0.5 g/kg) on prolactin levels was observed in both study groups. We found that alcohol (0.5 g/kg) had no significant effect on luteinizing hormone (LH) levels among subjects not using oral contraceptives, and observed a decline among subjects using oral contraceptives at midcycle. CONCLUSIONS: We suggest that the estradiol and progesterone effects are related to decreased steroid catabolism, resulting from the alcohol-mediated increase in the hepatic NADH-to-NAD ratio. The transient effect on prolactin levels may reflect acute changes in opioid and dopamine levels in the hypothalamus. The present findings regarding female sex steroids may be of relevance in the association between moderate to heavy alcohol consumption and the development of breast cancer.

Adult↗

Peripheral arterial disease as a predictor of outcome after renal transplantation.

Our aim was to assess the prevalence of symptomatic and asymptomatic peripheral occlusive arterial disease (POAD) in 129 consecutive diabetic (n = 34) and nondiabetic (n = 95) patients undergoing renal transplantation. The association of pre-existent POAD and complaints of claudication, lower limb amputations, and graft and patient survival were evaluated during a 5-year follow up. A questionnaire on walking capacity, ankle/brachial (ABI) and toe/brachial (TBI) pressure indices as well as the pulse volume recording (PVR) at the ankle were used to assess resting haemodynamics and the presence of POAD 4 days after the transplantation. Unquestionable ischaemia was encountered in 5 (4%) patients all with a history of intermittent claudication and an ABI equal or below 0.77. While using assessment methods not affected by vessel calcification, i.e. toe pressures and PVR damping, a many-fold frequency of arterial disease was observed when compared to previous studies. TBI below 0.65 was found in 11 of diabetic (32%) and in 15 of the others (16%), and a PVR amplitude below 5 min in 28 of diabetics (82%) and in 34 of non-diabetics (36%). During the 5-year follow up, abnormal TBI and PVR values and diabetes at the time of transplantation were the greatest risk factors for proximal foot amputations. The low TBI levels also indicated a shortened patient survival. However, transplant function was not affected by the presence of abnormal haemodynamic indices at the time of transplantation.

Adolescent↗

Circulating xanthine oxidase and neutrophil activation during human liver transplantation.

BACKGROUND & AIMS: Oxygen free radicals, generated by xanthine oxidase (XO) and activated leukocytes, are involved in reperfusion injury in experimental liver transplantation. The roles of XO and neutrophil activation during reperfusion in clinical liver transplantation were studied. METHODS: In 10 patients undergoing liver transplantation, we assessed plasma concentrations of circulating XO by enzyme-linked immunosorbent assay (ELISA), the purine metabolites hypoxanthine, xanthine, and urate by high-performance liquid chromatography, lactoferrin by ELISA, and malondialdehyde fluorometrically up to 48 hours postoperatively. RESULTS: During reperfusion after portal vein declamping, elevated plasma concentrations of XO (52.1 ng/mL [range, 8.0-440.1]), hypoxanthine (81.62 micromol/L [48.2-108.7]), xanthine (21.01 micromol/L [8.7-22.3]), and lactoferrin (532.6 ng/mL [370.4-1326.6]) were observed compared with the preoperative levels (0 ng/mL [0-12], 1.88 micromol/L [0.62-3.15], 0.95 micromol/L [0-0.41], and 164.3 ng/mL [73.7-334.1], respectively; all P < 0.05). No changes occurred in urate or malondialdehyde. After portal vein declamping, XO, hypoxanthine, and xanthine levels were substantially greater in the hepatic than portal vein (all P < 0.05). Marginal transhepatic differences occurred in lactoferrin. CONCLUSIONS: Reperfusion during liver transplantation is associated with liberation of xanthine oxidase, hypoxanthine, and xanthine from the liver into the circulation. During reperfusion, intravascular neutrophil activation takes place in the hepatic circulation.

Adult↗

Outcome of infrainguinal bypass surgery for critical leg ischaemia in patients with chronic renal failure.

OBJECTIVE: To determine whether infrainguinal bypass surgery is worthwhile in patients with critical limb ischaemia (CLI) and chronic renal failure. DESIGN: Longitudinal observational study. MATERIALS AND METHODS: Twenty-two patients with moderate renal failure indicated by serum creatinine level above 150 mumol/l, 10 patients with end-stage renal disease requiring dialysis, and three patients with functioning kidney transplant, underwent 39 bypass procedures for critical limb ischaemia. RESULTS: Six femoropopliteal, 14 femorocrural and 19 femoropedal bypasses were performed. The immediate, 1-month, and 1-year primary patency rates were 97%, 84% and 70%, respectively. The limb salvage was 93% at 1-month and 72% at 1-year follow-up. One-year patency and leg salvage rates were 81% and 79% in non-dialysis patients, and 47% and 37% in dialysis patients. At 1-year follow-up, 55% of surviving patients had salvaged limbs. None of the patients in dialysis was alive with salvaged legs 4 months after revascularisation. Among preoperative risk factors, only serum creatinine showed a statistical significance in predicting leg salvage and survival. CONCLUSIONS: As the outcome of patients on dialysis is very poor after infrainguinal bypass grafting, revascularisation is seldom indicated. On the contrary, leg salvage can achieve good results in patients not requiring dialysis.

Adult↗