Matti Kekki

Long-Term Course and Consequences of Helicobacter pylori gastritis Results of a 32-Year Follow-up Study

BACKGROUND The long-term course of Helicobacter pylori gastritis is not well known because there are few follow-up studies available, and the follow-up time has been short. METHODS The progression of H. pylori infection and chronic gastritis was retrospectively examined in 102 patients followed up for 32 years. In all patients a blind suction biopsy from the corpus mucosa was taken in 1952, and an endoscopic re-examination with biopsy specimens from the antrum and corpus was performed in 1983. RESULTS In the first examination 85 patients (83%) were H. pylori-positive as assessed from Giemsa-stained corpus mucosa specimens as compared with 70 H. pylori-positive patients (69%) at the end of the follow-up (1983). Two of the 17 patients who were initially H. pylori-negative became positive in 1983, implying an infection rate of 0.4% per patient-year. On the other hand, 17 of the 85 patients who were initially H. pylori-positive became negative in 1983, representing a disappearance rate of 0.6%. However, the stomach became completely normal in only eight cases, which represents a healing rate of 0.3% per patient-year. All patients with duodenal ulcer disease were H. pylori-positive at the first examination and remained so during the follow-up. In these patients chronic gastritis affected predominantly the antral mucosa, and corpus atrophy did not develop. Parietal cell antibodies appeared during the follow-up in six cases, and five of them were H. pylori-positive at the first examination. In most of these cases gastritis progressed into severe grades of corpus atrophy accompanied by the disappearance of H. pylori infection and normalization of the antral mucosa. CONCLUSIONS New H. pylori infection and complete healing of infected mucosa may occur in adult life, but this is rare. Duodenal ulcer disease is associated with persistent H. pylori infection and absence of corpus atrophy. The appearance of parietal cell antibodies leads to progression of corpus atrophy and disappearance of H. pylori.

Plasma triglyceride transport kinetics in diabetes mellitus

Plasma endogenous triglyceride transport has been measured in 74 adult patients with different types of diabetes and compared to similar data obtained in 35 healthy normoglyceridemic control subjects. The diabetic material was divided into subgroups by a number of criteria including ketoacidosis, insulin-dependence, relative body weight, control of blood glucose, and severity of hypertriglyceridemia. In ketoacidosis, a marked elevation of plasma triglyceride production rate was the rule, and this probably accounted for the moderate hypertriglyceridemia even though the fractional transport was simultaneously lowered. In uncontrolled but nonketotic juvenile-type diabetes the mean plasma triglyceride turnover rate and concentration were both significantly increased while the fractional turnover was in most cases within normal range. When the disease was brought into good control by insulin the production rate decreased but not completely in line with blood glucose. Patients with adult-onset-type diabetes showed also an increase of triglyceride turnover rate, and the magnitude of hypertriglyceridemia was consistent with this increment so that most patients were “on line” of the enzyme kinetic Michaelis curves extrapolated from the normal material. On the other hand, of nonketotic diabetics with severe hyperglyceridemia (more than 4.0 mM) some had an increased turnover rate, while others were characterized by a normal production rate. Therefore, it is probable that one minor group of diabetics has a true removal defect, while in other forms of diabetes, the hypertriglyceridemia, if present, is primarily due to enhanced hepatic secretion of triglycerides into plasma. The exogenous fat tolerance was tested in 15 uncontrolled diabetics and 10 control subjects with intravenous intralipid emulsion. The fractional disappearance rate was either normal or decreased in diabetes but, when compared at similar basal plasma triglyceride concentration, there was no difference in the elimination of exogenous particulate fat between diabetics and nondiabetics. The different mechanisms of hypertriglyceridemia associated with diabetes are discussed on the basis of the results obtained in this study. In this connection a new concept on the regulation of removal kinetics by plasma triglyceride production rate is suggested.

Plasma triglyceride metabolism in thyroid disease

Plasma endogenous triglyceride transport kinetics were determined in 16 hyperthyroid and in 12 hypothyroid patients and the results compared with those of euthyroid control subjects. In addition, the removal of exogenous particulate fat (Intralipid; Vitrum, Sweden) from the circulation and the postheparin plasma lipolytic activity (PHLA) were studied in these patients for further characterization of the alterations of plasma triglyceride metabolism in thyroid disease. In thyrotoxicosis the average plasma triglyceride level was slightly but significantly increased above that of control subjects. This change was associated with augmented production of triglycerides whereas the mean fractional removal rate was not different from normal. There was a significant linear correlation between the concentration and turnover rate of plasma triglycerides in both hyperthyroid and euthyroid subjects but the concentration/turnover rate ratio was less in the former group suggesting that the efficiency of removal of triglycerides from the circulation was improved in thyroid hyperfunction. The elimination of intravenously administered particulate fat occurred more rapidly in untreated hyperthyroid patients than in euthyroid control subjects. The mean PHLA was also above normal in thyrotoxicosis. Upon adequate treatment of the hyperthyroid state the fasting plasma triglyceride concentration was further increased. Hypothyroid patients showed another pattern of alteration of triglyceride kinetics. The synthesis of plasma triglycerides was normal but the fractional removal of both endogenous and exogenous triglycerides was markedly reduced and this change seems to account for the hypertriglyceridemia associated with thyroid hypofunction. The plasma PHLA was also clearly decreased in the hypothyroid state. Plasma FFA and glycerol levels were increased in hyperthyroidism and plasma FFA was slightly decreased in hypothyroid patients, but these variables were not significantly correlated with any parameter of triglyceride metabolism. Endogenous triglyceride turnover rate was significantly correlated with serum protein-bound iodine (PBI) and T3 uptake in thyrotoxicosis but not in hypothyroidism. Removal of exogenous fat was not related to postheparin plasma lipolytic activity but the fractional endogenous triglyceride transport showed a highly significant relationship to this lipase activity in a mixed group of hyper- and hypothyroid patients. The results suggest that thyroid hormones control both production and removal of plasma triglycerides. Different mechanisms for these interactions are considered.

Relation of plasma high-density lipoprotein cholesterol to lipoprotein-lipase activity in adipose tissue and skeletal muscle of man.

Lipoprotein-lipase activity (LPL) was measured in biopsies of adipose tissue and skeletal muscle of normal human subjects, and the results were related to concentrations of cholesterol and triglycerides in plasma lipoproteins. Adipose-tissue LPL activity was significantly higher in females than in males, whereas no sex difference was observed in skeletal-muscle LPL activity. A highly significant positive correlation was present between the plasma high density lipoprotein (HDL) cholesterol level and LPL activity in adipose tissue (r = +0.66, P less than 0.001) but not between HDL and skeletal-muscle LPL. The results suggest that the activity of LPL in adipose tissue and the rate of catabolism of triglyceride-rich lipoproteins might be one of the factors that determine the concentration of HDL in plasma and at least partly account for the known sex difference in plasma HDL level.

Plasma triglyceride turnover during use of oral contraceptives

Abstract The effect of oral contraceptives on the concentration, production rate, and removal efficiency of plasma triglycerides was studied in premenopausal women using an endogenous labeling of triglycerides with tritiated glycerol. Thirteen subjects were studied while receiving the drug and seventeen normal healthy females served as controls. In some instances the study was made both before and during the drug or repeated after discontinuation of the treatment. The elimination of triglycerides from the circulation was characterized using the Michaelis constant, Km, which gives the plasma concentration at half-maximal removal velocity. The control group showed a polymorphism of plasma triglyceride kinetics being composed of three subgroups which had different maximal turnover rates. Treatment with oral contraceptives was associated with highly significant increases of concentration, rate of production, and efficiency of removal of plasma triglycerides whereas the maximal turnover rate was apparently unaffected. Thus, the increase of plasma triglyceride concentration (average 1.5-fold) observed in women receiving oral contraceptives is accounted for by a much enhanced influx (average 1.9-fold). The influence of the latter is partly compensated by a simulataneous acceleration of triglyceride efflux, however. The effects are produced already by one cycle of treatment but almost no reversion of the changes can be observed at 1 mo after discontinuation of the drug. The triglyceride concentration and production rate were significantly correlated to the duration of intake of contraceptive preparations while the removal efficiency was not.

Atrophic chronic gastritis and intestinal metaplasia in gastric carcinoma. Comparison with a representative population sample

The occurrence of chronic gastritis and intestinal metaplasia (IM) was studied in 257 patients with gastric carcinoma (GC). In all cases biopsies were available from the benign mucosal area adjacent to the tumor, and in 139 patients from the antrum and/or body mucosa outside the tumor. The results were compared with endoscopically and bioptically examined noncancer controls representing a large Finnish population sample. For every GC patient, a control subject was matched by age and sex. In addition, a mean age‐adjusted score (AAS) of chronic gastritis, which expresses the progression of gastritis in GC patients as compared with that in the general population, was calculated for GC patients. The prevalences of chronic and atrophic gastritis in the antrum and body mucosa were similar in GC patients and controls when carcinoma cases were not more specifically classified according to histologic type or location of tumors. On the other hand, the location of the tumor showed a significant relation to gastritis: the progression of gastritis was more rapid (high mean AAS value) and the prevalence of atrophic gastritis was higher in the tumor‐affected area (i.e., in the antrum in patients with antral [distal] tumors; in the body in patients with body [proximal] tumors), than in the general population, but were similar in the tumor‐free area in both GC patients and controls. In the intestinal type of GC (IGC), the prevalence of chronic gastritis was higher and its progression was more rapid than in controls. In the diffuse type of GC (DGC), these correlations were less distinct. In GC patients, the IM adjacent to and outside the tumor area was significantly more common and extensive than in the corresponding area of controls, and a significant positive correlation was present between the location of the tumor and the distribution of IM. Like gastritis, the IM showed a closer relationship to IGC than to DGC. In all cases of GC and particularly of IGC, the antral mucosa tended to be more severely affected by gastritis and IM than the body mucosa, i.e., the prevailing type of gastritis found in this GC series was that morphologically corresponding to the so‐called B‐type of chronic gastritis.

Age- and Sex-Related Behaviour of Gastric Acid Secretion at the Population Level

Pentagastrin-stimulated gastric acid output and the histology of the antral and body mucosa were examined in 72 computer-selected probands and their 365 relatives, altogether 437 cases. The frequencies of upper abdominal complaints, peptic ulcer and hiatal hernia, and blood group distribution were comparable with those of the population at large. Acid output, expressed as mmol/h, mmol/h/kg of total body weight (TBW), mmol/h/kg of lean body mass (LBM), and mmol/h/kg of fat-free body weight (FFB), correlated with the changes in the body mucosa but not with those in the antrum. Acid output was lower in females than in males when expressed as mmol/h or mmol/h TBW but not when expressed in terms of FFB, which better than LBM accounts for the variation in the gastric surface area and, in this manner, for that of the parietal cell mass. This suggests that the lower acid output in females is due to a smaller gastric surface area and correspondingly smaller parietal cell mass rather than to a lower reactivity of the cells to stimulation. Acid output decreased with increasing age in both sexes, and this was due to a concomitant increase in the incidence and severity of atrophic changes in the body mucosa. An age-related decrease in acid output was not seen in males with a normal body mucosa. In females with a normal body mucosa, however, output expressed in terms of FFB showed a significant increase with age. The reason for this increase is not clear. In males and females with superficial gastritis of the body mucosa acid output decreased with increasing age regardless of the formulation used.

Lipoprotein-lipase action determining plasma high density lipoprotein cholesterol level in adult normolipaemics

In a series of healthy normolipaemic, adult subjects, plasma triglyceride turnover, heparin-releasable lipoprotein lipase (LPL), and plasma HDL cholesterol were determined. Strong correlations were found to exist between the fractional removal rate of plasma triglycerides (FTR) or LPL as one variable and HDL cholesterol as the other, whereas the triglyceride turnover rate (TR) did not correlate with HDL cholesterol. It is concluded that lipoprotein lipase action is largely responsible for the formation of HDL cholesterol in the blood stream.

Plasma Triglyceride Metabolism in the Adult Nephrotic Syndrome

Abstract. The kinetic parameters of plasma triglyceride metabolism were determined in 14 adult subjects with the nephrotic syndrome by endogenous labelling of circulating triglyceride with tritiated glycerol. The triglyceride production (turnover) rate and the apparent Km of removal were calculated from the slope of the radioactivity disappearance curve and compared to a normal control material studied previously. Plotting of the individual data in a log scale of triglyceride concentration versus turnover with the normal area and saturation curves in the background allowed a detailed characterization of the nature of kinetic alterations occurring in disease. It was found that in the majority of cases with the nephrotic syndrome the plasma triglyceride concentration and rate of influx are slightly above normal. However, the apparent Km of removal was significantly increased suggesting that efflux may also be somewhat impaired. In four cases the plasma triglyceride was produced at a rate which exceeded the value predicted by the normal saturation curves and it is believed that an uncontrolled overproduction of plasma triglyceride was present in these cases.—Complete remission of disease in one case brought both triglyceride concentration and turnover rate rapidly to normal values. An eight‐hour infusion of human serum albumin in another patient promptly caused a return of high triglyceride turnover to normal.— The primary change behind the nephrotic hypertriglyceridaemia seems to be a controlled increase of plasma triglyceride synthesis. In some cases, however, this overproduction occurs in an uncontrolled fashion and in a number of patients decrease of removal efficiency contributes to the development of hyperglyceridaemia. All of these changes can be explained on the basis of an increased FFA/albumin molar ratio in plasma giving rise to the elevation of unbound FFA fraction.

Kinetic behaviour of 131i-labelled myoglobin in human beings☆

Abstract The kinetic behaviour of extracellular myoglobin was studied by means of [ 131 I]myoglobin in four healthy persons. Less than 3% of the injected myoglobin was found in the urine, the rest being most probably catabolized by the kidney. The degradation rate was rather rapid. The time in which all myoglobin in the i.v. compartment was catabolized varied from 49 to 224 min. The extravascular compartment was rather large indicating a relatively high concentration of myoglobin in lymphatic and extracellular spaces. The intravascular space contained from 4 to 13.4% of the extracellularly circulating myoglobin.