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The Catharantus derivatives are microtubule antagonists employed in immunosuppression and chemotherapy of neoplasms. The role of cytoplasmic microtubules in polymorphonuclear leucocyte (PMN) adherence was studied by means of therapeutic concentrations of the Catharantus derivatives vincristine, vinblastine and vindesine. PMN adherence was measured as retention on an albumin-coated glass surface. PMN adherence was reduced by 4-54% by the Catharantus derivatives, as compared with control values. The suppression of adherence was statistically significant. Since the Catharantus derivatives are microtubule antagonists, it is reasonable to assume that PMN adherence is a partially microtubule-dependent process. It is suggested that reduction of PMN adherence could account for at least part of the immunosuppressive properties of the Catharantus derivatives.

alpha 1-Antitrypsin (AAT) deficiency of phenotype PiZ and idiopathic hemochromatosis (IH) predispose to the development of cirrhosis and liver cell carcinoma. Several reports have suggested an association between these two inborn errors. To elucidate this question we used a monoclonal antibody against the PiZ gentic variant of AAT to analyze and compare the PiZ gene frequency in an area (county of Jämtland in Central Sweden) with a high, and another area (the city of Malmö in Southern Sweden) with a low IH prevalence. The PiZ gene frequencies did not differ between the areas. We also analyzed sera from 27 unrelated adult males with hemochromatosis diagnosed in the high IH area for the presence of the PiZ gene product but none was a carrier of the PiZ allele. These findings strongly refute any association between. AAT deficiency and IH.

Theoccurrence of PAS-positive, diastase-resistant, inclusion bodies in hepatocytes has been used as a marker of heterozygous (Pi MZ) alpha1-antitrypsin deficiency in order to study the frequency of lung, liver and malignant disease in a consecutive autopsy material from a well defined population. Typical PAS-positive inclusion bodies were found in the liver in 26 (3.7%) of the 700 cases studied. In these 26 subjects both liver (cirrhosis or fibrosis) and lung disease (emphysema) were significantly more prevalent (p less than 0.001) than among PAS-negative controls. The prevalence of malignant disease did not differ between the groups. The results are consistent with the concept that heterozygous (Pi MZ) alpha1-antitrypsin deficiency predisposes to both liver and lung disease but does not influence the survival rate.

Clinical, laboratory and follow-up results in 13 patients with primary biliary cirrhosis (PBC) collected during the last 10 years in a well defined population of 250,000 inhabitants are presented. The mean observation time was 5.5 years. 77 percent of these patients have been asymptomatic for many years. Characteristic laboratory features in asymptomatic patients are high alkaline phosphatases and glutamyl transpeptidases and very high levels of polyclonal IgM. ESR is often increased. Signs of active cell destruction are slight and functioning cell mass is well preserved. High titers of mitochondrial antibodies are consistently present. Needle biopsy is seldom sufficient for diagnosis but permits staging of the disease. There is no correlation between clinical features and histological evolution stage. Compared with a preceding 10-year period, the incidence of PBC has risen threefold. This increase can be fully explained by the extended use of laboratory facilities, resulting in the detection of asymptomatic patients.

Serological and pathological findings in 21 patients with primary Sjögren's syndrome (primary SS) were compared with those in 32 patients with primary biliary cirrhosis (PBC). In ELISA, anti-SS-B/La antibodies were detected in sera from 14 (67%) of the patients with primary SS, but only from 12 (38%) of those with PBC. With the Ouchterlony test, anti-SS-A/Ro antibodies were found in sera from 15 (71%) of the primary SS patients, but in no PBC patient. Of those PBC patients investigated prospectively with objective tests, four of 11 (36%) had keratoconjunctivitis sicca, and five of 15 (33%) had pathological sialometry results. In contrast, all PBC patients but one (i.e., 14 of 15 or 93%) showed evidence of focal sialadenitis. In immunochemical study of PBC patients, IgM immunoreactivity was found in the stroma, particularly adjacent to excretory ducts and acini in salivary glands (5 of 5), whereas no such IgM deposits were observed in patients with primary SS (3 of 3), nor in healthy controls (n = 20). We conclude that the frequency of anti-SS-A/Ro and anti-SS-B/La antibodies in serum is lower in PBC patients than in patients with primary SS. The incidence of focal sialadenitis is high in PBC, though only one third of the PBC patients studied here showed clinical evidence of glandular dysfunction. With immunochemical techniques, sialadenitis associated with PBC is distinguishable by its significant IgM reaction from sialadenitis in primary SS.

A patient with widespread acanthosis nigricans is described. No abdominal tumour was found. Explorative thoracotomy disclosed numerous enlarged lymph glands containing squamous cell carcinoma. The left lung was removed but meticulous search did not disclose any tumour. The glands were removed as radically as possible. After the operation the skin improved and the lesions have disappeared completely. The observation time is over three years.

Nonalcoholic steatohepatitis is a rare complication of obesity with laboratory and histological features indistinguishable from alcoholic hepatitis. Three patients with 50-60% overweight and steatohepatitis are reported. All responded with normalization of the biochemical and/or histological changes after modest weight reduction.

We studied patients and their relatives with partial deficiency, approximately 50% of normal plasma levels, of alpha 1-antichymotrypsin (ACT), an acute phase reactant with anti-cathepsin G activity. Six of eight ACT deficient individuals, over 25 years of age, had liver and three of eight lung manifestations, varying from severe disease to subtle laboratory abnormalities. The ACT of deficient individuals (who are heterozygotes for a rare gene, q = 0.003) had normal crossed immunoelectrophoretic properties. The abnormal gene is inherited in an autosomal, dominant way. The results suggest that deficiency of this antiprotease, which also has immune response modulating properties, may predispose to liver and lung disease.

Hyperosmolar non-ketotic coma in diabetes is a life-threatening condition. We describe three patients, aged 59-67 years, who developed hyperosmolar coma during the first ten days after admission for stroke. Common to all three were normal plasma osmolality and slightly elevated plasma creatinine levels on admission, treatment with diuretics, parenteral dextrose administration before and low urinary glucose output during the coma. In the five days preceding the coma, total fluid deficits were 3.8, 6.5 and 9.4 1, respectively. In one patient the rate of glucose delivery had clearly exceeded utilization during adequate insulinization, in another a marked reduction in urinary glucose output preceded extreme hyperglycaemia and coma. Two of the three patients died, both from extensive thrombus formation in cerebral arteries and multiple emboli to the lungs. We conclude that enhanced endogenous glucose production and reduced renal clearance of glucose may contribute to precipitate hyperosmolar non-ketotic coma. A close monitoring of fluid and dextrose administration seems mandatory in diabetic stroke patients, in particular if renal function is impaired or if diuretics are given. Insulin treatment should be considered in all diabetic patients during the first days after a stroke.

Sixty-two patients with ischemic stroke possibly due to embolism of cardiac origin were investigated by pulmonary artery-cineangiography (PACAC) and echocardiography (UCG) to detect intracardiac thrombi. The proportion of intracardiac thrombi found by PACAC was 31% and by UCG 15%. The presence or absence of atrial fibrillation correlated well with PACAC findings of an intraventricular clot but poorly with UCG. Similarly, there was a significant association between ischemic heart disease and intraventricular thrombi detected by PACAC investigations but not with the results obtained by UCG. PACAC seems superior to UCG in the detection of intracardiac thrombi after possible embolic stroke.

alpha 1-Antitrypsin (AAT) deficiency in adults predisposes to lung and liver disease, but its natural history is incompletely known. To better characterize the liver disease, all known deceased adult Swedish patients known to us with homozygous (PiZZ) AAT-deficiency, who had undergone autopsy during the 20-year period 1963-82 were reviewed. Of 94 such patients, 35 had cirrhosis (27 males and eight females) with a mean age at death of 65.5 +/- 10.5 (SD) years compared to 53.6 +/- 12.8 years (p less than 0.01) for the 59 non-cirrhotic patients. The longer survival suggests less severe lung disease in the cirrhotic group. Clinically these patients most frequently presented with ascites or other signs of portal hypertension. Evidence of alcohol overconsumption, chronic viral hepatitis, or autoimmune disease was rare. Aside from low plasma AAT levels, laboratory and other clinical features were indistinguishable from those of decompensated cirrhosis of any etiology. The prognosis was generally grave with a mean survival of two years after diagnosis. Fourteen of the 35 cirrhotics (10 males and four females) had primary liver cancer (PLC) at autopsy. We conclude that cirrhosis and PLC are more frequent complications in elderly patients with AAT-deficiency than was previously known. These complications had a marked male predominance.

In a prospective study of the incidence of deep vein thrombosis (DVT) after stroke, and the prophylactic effect of dextran, 50 patients, admitted with a diagnosis of cerebral infarction with paresis of the lower extremity within the first 48 hours, were randomly allocated to treatment or non-treatment groups. The treatment group received 500 ml of dextran 40 on admission and on days 1 and 2, and 250 ml on days 4 and 6. Venesection was performed on admission and if necessary on day 1. The control group received no dextran or venesection. DVT was diagnosed with the 125I-fibrinogen test during the first ten days. The incidence of DVT was 54% in the treatment group and 50% in the control group. There were no statistically significant differences between the groups regarding number of DVTs needing treatment, number of positive scanning points or number of days for scan to become positive. Lethal pulmonary emboli occurred in one treated and in three control patients, respectively. Age and progress of neurologic symptoms predisposed for the development of DVT. The high incidence of DVT in stroke patients indicates the need for prophylactic routines.

Propafenone, a new class I antiarrhythmic drug, given as a bolus injection followed by oral medication, or lidocaine were given to 20 consecutive patients admitted with chest pain suggesting acute myocardial infarction and showing high grades, i.e. multiform, pairs or R-on-T premature ventricular complexes or short runs of ventricular tachycardia. Before institution of therapy the mean number (+/- 1 SD) of premature ventricular contractions (PVCs) per hour was 169 +/- 123 in the lidocaine group and 324 +/- 440 in the propafenone group. During the next 24 hours lidocaine reduced the numbers of PVCs by 73% and propafenone by 75%. The mean number (+/- 1 SD) of 5-minute periods with high grade PVCs was 4.3 +/- 2.9 in the lidocaine group and 5.8 +/- 4.5 in the propafenone group. During therapy this number was equally reduced in both groups to 2.4. One patient in the lidocaine group developed ventricular fibrillation and three patients in the propafenone group were excluded because of increasing numbers of PVCs. One patient in the propafenone group showed a torsade-de-pointes ventricular tachycardia.

A thyrotropin-releasing hormone (TRH) test with serum thyroid-stimulating hormone (TSH) assays was performed in 22 euthyroid stroke patients without thyroid disease and the results were compared with those in 17 age-matched euthyroid controls. Basal and maximum TSH levels after TRH injection were significantly lower in the stroke group without elevation of basal serum thyroid hormone levels. There was a tendency towards an inverse relationship between TSH levels and the degree of pareses of the extremities. The test was repeated in 7 stroke patients 3-4 months after the onset of stroke with essentially the same results. The abnormal TSH parameters in stroke patients seem to be the result of the brain lesion per se.

Screening for idiopathic hemochromatosis (IH) in 941 men, 55 years of age, did not reveal any individual with both biochemical abnormalities and liver iron content compatible with homozygosity for the IH gene. In a large autopsy series of 8 834 males representative of southern Sweden, we found classical hemochromatosis in 0.1%. The results are in contrast with the high frequency of homozygous IH found in the county of Jämtland in central Sweden. We suggest that the difference in gene frequency is a result of enrichment of the recessive IH gene in the Jämtland population by the mechanisms of sampling and drift. We conclude that population screening for early IH in southern Sweden is not worthwhile.

Immunofluorescence studies on skin biopsies from 14 patients with primary biliary cirrhosis (PBC) showed granular papillary deposition of IgM in all. In addition, 6 patients had C3 deposition. Control patients with various other liver diseases, idiopathic high plasma levels of igM and extrahepatic cholestasis were only sporadically positive for IgM and not at all for C3. IgM deposition in dermal papillae in PBC does not merely reflect high plasma IgM levels or cholestasis but probably represents an immunochemically abnormal IgM population.

The plasma acute phase reactant pattern was studied in 124 patients with liver disease and 16 healthy individuals undergoing liver biopsy, alpha 1-Antitrypsin levels were found to correlate positively with the extent of hepatocellular damage, inflammatory activity and total biopsy score. Haptoglobin levels correlate negatively with these parameters and particularly with characteristics conducive to portal hypertension. Orosomucoid and fibrinogen were unaffected by extent of disease and activity. These changes result in a typical acute phase reactant pattern, seen most frequently in viral hepatitis and chronic active hepatitis and less frequently in alcoholic liver disease. When present, it has a high specificity and predictive value for detection of liver disease.

We have analyzed the prevalence of pernicious anemia (PA) in all patients with autopsyverified gastric carcinoma (GC) registered during 1958-76 in a Swedish city, with one Department of Pathology serving approximately 240 000 inhabitants and with a high autopsy frequency. The prevalence was compared to that in a reference group of 917 sex- and age-matched individuals without GC. PA was found in 19 persons, 2.1%, (7 males and 12 females) in the GC group and in 13 persons, 1.4%, (5 males and 8 females) in the reference group. This difference is not significant (p less than 0.15). After exclusion of individuals with PA known for less than 5 years before death, the corresponding figures were 16 in the GC group against 8 in the control group. This difference is significant (p less than 0.05). Regarding individuals with a diagnosis of PA for greater than 10 or greater than 15 years, the prevalence was twice as high in the GC as in the reference group. The differences were again insignificant (p less than 0.10). PA as a risk factor for the development of GC has been overestimated probably due to inadequate reference groups. Only 2% of all GCs are associated with PA. Large-scale preventive search for GC in PA patients is thus unjustified.

A 57-year-old woman, treated for a large anterior transmural myocardial infarction, was readmitted after 8 weeks because of progressive cardiac failure. Chest X-ray showed cardiomegaly with an atypical cardiac silhouette. Two-dimensional echocardiography disclosed a large left ventricular pseudoaneurysm. The patient underwent resection of the false aneurysm with repair of the left ventricular wall and recovered gradually. Different methods for diagnosing pseudoaneurysm are discussed.

Risk factors of death for a population of 409 patients with well-defined cerebrovascular disease (patients with subarachnoidal hemorrhage excluded) admitted to the Stroke Unit were studied with the aid of the life table technique, log rank test, and multivariate analysis with BMDP's program for regression on the survival curves with Cox's proportional hazard model. The estimated proportion of survivors was 77% after three months, 69% after one year, and 32% after five years. Patients with intracerebral hemorrhage and embolic cerebral infarction had the worst outcome. Impaired consciousness on admission was the most important risk factor of death followed by high age, previous cardiac failure, diabetes mellitus and male sex.

The clinical and echocardiographic features of cardiac amyloidosis may closely resemble those of hypertrophic cardiomyopathy, and the disorders may thus be mixed up. The present study was undertaken in an attempt to identify features separating the two conditions by analysis of electro- and echocardiographic findings in patients with familial amyloid polyneuropathy and hypertrophic cardiomyopathy. Twenty-nine patients with familial amyloidosis and 22 with hypertrophic cardiomyopathy were studied. Particular attention was given to the sum of the S wave in V1 and R wave in V5 or V6, the echocardiographic left ventricular mass and cross-sectional area, the presence or absence of asymmetrical septal thickening, granular and sparkling myocardial appearance, thickened heart valves, systolic anterior motion of the mitral valve, and pericardial effusion. A granular and sparkling appearance of the myocardium and thickened heart valves were found to be the best predictors of cardiac amyloidosis, while low QRS amplitudes in relation to echocardiographic left ventricular mass and a pericardial effusion seemed less important. The presence of systolic anterior movement of the mitral valve, a large left ventricular mass and a sum of S in V1 and R in V5 or V6 greater than 35 mm indicated hypertrophic cardiomyopathy. When the four strongest predictors (left ventricular mass, thickened heart valves, a granular sparkling myocardial appearance, and systolic anterior movement of the mitral valve) were used to reclassify the present patients, 28 of 29 amyloidosis patients and 21 of 22 patients with hypertrophic cardiomyopathy were correctly categorized. Noninvasive methods may thus be useful for detecting the myocardial infiltrative process, and cardiac amyloidosis may be confidently diagnosed by typical noninvasive findings together with histopathological documentation of amyloid in an organ other than the heart.