Tolerance to 3,4-methylenedioxymethamphetamine in rats exposed to single high-dose binges.

3,4-Methylenedioxymethamphetamine (MDMA or ecstasy) stimulates the transporter-mediated release of monoamines, including 5-HT. High-dose exposure to MDMA causes persistent 5-HT deficits (e.g. depletion of brain 5-HT) in animals, yet the functional and clinical relevance of such deficits are poorly defined. Here we examine functional consequences of MDMA-induced 5-HT depletions in rats. Male rats received binges of three i.p. injections of MDMA or saline, one injection every 2 h; MDMA was given at a threshold pharmacological dose (1.5 mg/kgx3, low dose) or at a fivefold higher amount (7.5 mg/kgx3, high dose). One week later, jugular catheters and intracerebral guide cannulae were implanted. Two weeks after binges, rats received acute i.v. challenge injections of 1 and 3 mg/kg MDMA. Neuroendocrine effects evoked by i.v. MDMA (prolactin and corticosterone secretion) were assessed via serial blood sampling, while neurochemical effects (5-HT and dopamine release) were assessed via microdialysis in brain. MDMA binges elevated core temperatures only in the high-dose group, with these same rats exhibiting approximately 50% loss of forebrain 5-HT 2 weeks later. Prior exposure to MDMA did not alter baseline plasma hormones or dialysate monoamines, and effects of i.v. MDMA were similar in saline and low-dose groups. By contrast, rats pretreated with high-dose MDMA displayed significant reductions in evoked hormone secretion and 5-HT release when challenged with i.v. MDMA. As tolerance developed only in rats exposed to high-dose binges, hyperthermia and 5-HT depletion are implicated in this phenomenon. Our results suggest that MDMA tolerance in humans may reflect 5-HT deficits which could contribute to further dose escalation.

[The life of Joseph Haydn from a medical point of view (author's transl)]. / Joseph Haydns Leben aus medizinischer Sicht

Joseph Haydn (1732 to 1809) had hardly been troubled by any illness of note, apart from a chronic nasal polyp until 1799. During the composition of the oratoria "The Seasons" (1799 to 1801), the signs of cerebral arteriosclerosis with cardiac insufficiency made their appearance. Haydn's creative strength subsequently declined rapidly and he was virtually unable to compose any more after he had finished "The Seasons" until his death in 1809. The plan to compose a third oratoria "The Last Judgement" ended abortively. Haydn himself suffered acutely from the inactivity imposed on him by the illness, as documented by various sources. Hadyn remained fully conscious right up to the time of his death, which presumably resulted from cardiac failure. Haydn's grave was ransacked only a few days after the funeral and his skull was snatched. It has been finally restored to his resting place in Eisenstadt only as recently as 1954 after a protracted and devious journey.

Genetically correlated effects of selective breeding for high and low methamphetamine consumption.

Improved prevention and treatment of drug addiction will require deeper understanding of genetic factors contributing to susceptibility to excessive drug use. Intravenous operant self-administration methods have greatly advanced understanding of behavioral traits related to addiction. However, these methods are not suitable for large-scale genetic experiments in mice. Selective breeding of mice can aggregate 'addiction alleles' in a model that has the potential to identify coordinated effects of multiple genes. We produced mouse lines that orally self-administer high (MAHDR) or low (MALDR) amounts of methamphetamine, representing the first demonstration of selective breeding for self-administration of any psychostimulant drug. Conditioned place preference and taste aversion results indicate that MAHDR mice are relatively more sensitive to the rewarding effects and less sensitive to the aversive effects of methamphetamine, compared to MALDR mice. These results validate the oral route of self-administration for investigation of the motivational effects of methamphetamine and provide a viable alternative to intravenous self-administration procedures. Gene expression results for a subset of genes relevant to addiction-related processes suggest differential regulation by methamphetamine of apoptosis and immune pathways in the nucleus accumbens of MAHDR and MALDR mice. In each line, methamphetamine reduced an allostatic state by bringing gene expression back toward 'normal' levels. Genes differentially expressed in the drug-naï ve state, including Slc6a4 (serotonin transporter), Htr3a (serotonin receptor 3A), Rela [nuclear factor kappaB (NFkappaB)] and Fos (cFos), represent candidates whose expression levels may predict methamphetamine consumption and susceptibility to methamphetamine reward and aversion.

[Expert judgement in liver disease (author's transl)]. / Begutachtung von Leberkranken.

Expert judgement on duration and extent of unfitness for work in various liver diseases is rather uniform nowadays. Problems are more often encountered when causal relationships have to be established or excluded, especially in medical personal suffering from liver disease. Since several years, however, the medical expert may relay upon more sophisticated diagnostic tools supplied by progress of virology of hepatitis. Further improvement of these tools within the next years is to be expected. This progress may as well facilitate judgement of causal relationships between effects of diseases occurred during the war and liver disease of recent origin. The medical expert in the field of hepatology has to be well acquainted with all recent knowledge and research results in virus hepatitis.

[Geriatric pancreatitis]. / Alterspankreatitis.

There is some doubt whether a clinical entity like old age pancreatitis exists. According to Ammann, a so-called senile chronic pancreatitis can be differentiated from chronic alcohol-induced pancreatitis. With increasing incidence, secondary concomitant pancreatitis is seen in old patients, initiated by disorders of the biliary system. Whereas in senile chronic pancreatitis therapy consists of enzyme substitution and compensation of deficiency syndromes, therapy of secondary pancreatitis is aimed at basic disorders like choledocholithiasis, papillary sclerosis and stenosis, juxtapapillary diverticula and peptic ulcers in stomach and duodenum by surgical or endoscopic-operative means.

[Bed rest, diet and working capability in liver disease (author's transl)]. / Bettruhe, Diät und Arbeitsfähigkeit bei Lebererkrankungen.

General views concerning bed rest, diet and working capability in liver disease have changed during the last years. Rigorous bed rest in acute viral hepatitis is necessary only for short periods of time; it is necessary in chronic liver disease only in rare cases and during the terminal stage, respectively. A liver diet does not exist. Normal palatable nutrition is completely adequate in liver disease. Restriction of protein and sodium chloride intake is indicated only in cases with incumbent coma or with ascites. Patients suffering from acute viral hepatitis are incapable of working; however, they can go back to work a few weeks after the acute stage. Estimation of disability to work in patients with chronic liver disease may be difficult; no general rules can be given; in chronic active hepatitis disability is proportional to the activity of the disease and may range from 20-100%. Fatty liver without inflammatory changes does not influence working capability.

[Etiology and management of habitual constipation (author's transl)]. / Ursachen und Behandlung der habituellen Obstipation

Habitual constipation is present, if defecation occurs because of prolonged retention of stool in the colon less than three times per week. Motility of the intestine is increased in these cases, not decreased as has been thought for long time. Several factors of modern civilization favor habitual constipation, e.g. nutrition devoided of poorly digestible ingredients, and lack of physical exercise. The diagnosis of habitual constipation should only be made after careful exclusion of all organic causes by means of x-ray and endoscopic examination. Therapy is conservative in most cases. The diet ought to be rich in indigestible ingredients; eating and defecation habits have to be adapted to a regular pattern. Hydrophilic colloid laxatives may be used as well as in a limited extent laxatives effective on an osmotic basis. Laxatives acting more drastically or being effective upon contact with the intestinal mucosa are not suited for long-term therapy of constipation. Surgery is indicated only in a few cases.

[Posthepatitic cirrhosis of the liver without symptoms: observance about 22 years (author's transl)]. / Posthepatitische Leberzirrhose ohne Symptome. Verlaufsbeobachtung über 22 Jahre

There are only a few studies about sufficiently documented posthepatitic cirrhosis of the liver for more than two decennaries. Therefore we report about a patient, who showed at laparoscopy in 1954 a posthepatitic cirrhosis of the liver. Since the end of the fifty years the laboratory findings had normalized and the patient worked hard and felt himself well. At a control laparoscopy with liver biopsy in 1975 a complete inactive cirrhosis of the liver was confirmed. Blood samples were normal and HBsAG seronegative. Therefore, it seems to be possible, that in some few cases cirrhosis of the liver remaining without clinical symptoms over many years - for example in late prisoners of the war, who returned home with an inactive full developed cirrhosis of the liver - but now is detected.

[Sonographically assisted liver biopsy--replacement for blind needle biopsy?]. / Die sonographisch assistierte Leberbiopsie - Ablösung der blinden Leberpunktion?

Since the beginning of 1980 the authors have performed upper-abdominal ultrasound examination immediately preceding percutaneous needle biopsy (after Menghini), previously performed "blind". Knowledge of the particular liver topography made it possible to perform reliably punctures with only a small number of multiple punctures (6.4%) being required, suitable biopsies more often being obtained than under laporoscopic control. Compared with 354 consecutive blind liver biopsies, guided biopsy caused pain from the puncture in 1.9% (previously 5.9%), with a reduction of need for analgesics from 4.5% to 1.1%. The rate of more serious complications was reduced from five (1.4%) to one (0.2%), although as a result of ultrasound the indications for percutaneous liver biopsy were more frequent, since numerous "classical" contra-indications could be ignored. Blind liver biopsy should thus be abandoned for ultrasound-guided percutaneous puncture.

[Melanosis coli(author's transl)]. / Melanosis coli

Melanosis coli is caused by deposits of malanin- or lipofuscin-containing pigments in the colon mucosa; it is a conspicuous sign of long standing abuse of anthrachinonic laxatives. Melanosis coli can be easily diagnosed during rectoscopy, using morphological as well as histological criteria; nevertheless this condition is often overlooked or goes unnoticed. Abuse of laxatives, which is denied or concealed rather often by patients, does however explain in many cases otherwise unexplained abdominal complaints. Four cases are reported demonstrating the diagnostic significance of colonic melanosis.

[Whipple's disease]. / Beitrag zur Whippleschen Krankheit

Whipple's disease is characterized morphologically by macrophages in the small intestine which store PAS-postive material, as well as coarsening and atrophy of the intestinal villi, with pseudocystic cavitations. Without treatment it ends fatally due to irreversible diarrhoea and cachexia. Until 1963, only 90 cases had been diagnosed, most of them at autopsy. Intestinal biopsy has facilitated the diagnosis in life. Treatment with antibiotics results in dramitic improvement and remission for many years. From this an at least partial bacterial cause of the disease has been deducted, but it has not been possible so far to identigy more precisely any causative bacteria. Two cases of Whple's disease with some special features are reported. Both occurred in women (previous reports were almost entirely of men). The severely ill patients were cured by tetracycline within a few weeks and have remained completely well at follow-up examinations. The morphological changes in the intestinal mucosa had partially regressed.

[Nodular lymphoid hyperplasia of the small intestinal, hypogammaglobulinemia and rheumatoid arthritis (author's transl)]. / Lymphfollikuläre Hyperplasie des Dünndarms mit Hypogammaglobulinämie und rheumatoider Arthritis.

A case report is given of a patient with intestinal nodular lymphoid hyperplasia, hypoimmunoglobulinemia and seronegative rheumatoid arthritis with extensive deformation of joints, who was diagnosed and followed for 10 years clinically and by repeated endoscopic and bioptic examinations. It could be shown for the first time by temporary omission of corticosteroids that continuous therapy with corticosteroids is indispensable in this disease.

[Coincidence of chronic pancreatitis and liver cirrhosis in alcohol abuse. A x-ray and histomorphological study]. / Koinzidenz von chronischer Pankreatitis und Leberzirrhose bei Alkoholabusus. Eine röntgen- und histomorphologische Studie.

We conducted a retrospective study in 112 chronic alcoholics in order to evaluate the incidence of simultaneous damage of both pancreas and liver. In all patients, an endoscopic retrograde pancreaticography (ERP) and a liver biopsy were performed. 65 patients had alterations of the pancreatic ducts compatible with the diagnosis of chronic pancreatitis. 30,7% (20/65) suffered from an additional alcoholic liver cirrhosis. This is a much more frequent association than presumed by H. Sarles et al. and Ammann et al. When the diagnosis was established, the average age of the group with chronic pancreatitis and liver cirrhosis was the same as in patients with chronic pancreatitis without cirrhosis (43,3 versus 42,4 years). Routine laboratory findings were of little value in comparison to the morphological findings.