Pain perception of intravenous heroin users on maintenance therapy with levomethadone.

Methadone is a very potent analgesic drug. Accordingly, maintenance therapy of heroin addicts with methadone may conceal pain producing processes. Here we report on the pain perception of 42 patients on a levomethadone maintenance treatment for intravenous heroin users. Pain perception was measured by single-blind, non-invasive pressure stimulation of the nociceptors located in the dorsal extension aponeurosis and the underlying periosteum of the middle phalanx of a digit before and respectively 1,2, and 4 hours after oral routine drug administration. Measures were related to the individual levomethadone plasma levels. Under steady-state conditions, the pain perception of the patients did not differ from a drug-free placebo control group and was not related to individual levomethadone plasma levels, although an analgesic effect in the reabsorption phase was observed. It is concluded that the individual pain perception of maintained patients is adapted to a normal response range and that even prolonged opioid consumption does not diminish dynamic analgesic responsiveness to levomethadone.

Pharmacokinetic and pharmacodynamic interactions in an outpatient maintenance therapy of intravenous heroin users with levomethadone.

The plasma levels of 42 patients on a levomethadone maintenance treatment programme for intravenous heroin users were measured before and, respectively, 1, 2 or 4 hours after oral routine administration and related to the individual additional drug usage (detected by urine drug screening), liver function, side-effects and withdrawal symptoms. In general, accelerated levomethadone metabolism induced by additional misuse of benzodiazepines, barbiturates and opiates resulted in significantly lower plasma levels of the substitute. In particular, high gamma-glutamyltransferase activity was related to benzodiazepine consumption. On the other hand, an impaired liver function reflected by increased beta-globulins resulted in an insufficient body clearance and drug accumulation. Major side effects, such as sweating, were not related to plasma levels whereas withdrawal symptoms like diarrhoea or "feeling cold" correlate with lower plasma concentrations. It is concluded that polydrug misuse in the methadone maintenance therapy creates a vicious circle of enzyme induction, thus increasing "instrumental drug utilization". However, underestimated maintenance dosage may lead to additional drug consumption resulting, finally, in therapeutic failure.

[Diaplacental poisoning with narcotics and alcohol in newborn infants]. / Diaplazentare Intoxikation mit Rauschgift und Alkohol bei Neugeborenen.

In seven neonates, clinical symptoms detected on the first day of life appeared to show that toxicological investigations of the blood and urine were indicated in the mother and baby. In five mothers, there was known drug consumption. The investigations revealed toxic concentrations of morphine or cocaine in all babies; these could also be detected at comparable levels in the mothers. In a further case, a perinatal death must be attributed to acute diaplacental alcohol intoxication. The significance of toxicological investigations in neonates and perinatal deaths is also indicated.

[Putrefaction-induced changes in the concentration and temporal detectibility of carbon monoxide in cadaveric blood samples]. / Fäulnisbedingte Konzentrationsänderungen und zeitliche Nachweisbarkeit von Kohlenmonoxid in Leichenblutproben.

Eighty-five blood samples with COHb concentrations of 40% and 70% were allowed to putrefy in order to measure the time-dependent changes in COHb values. The samples not hermetically closed had been stored at 6 degrees C and 20 degrees C. GC and photometric methods were applied. Two graphs show that after 15 days (40% COHb) and after 30 days (70% COHb), the COHb concentrations decreased to half at 20 degrees C. Corresponding decreases at a storage at 6 degrees C could be observed after 1 year. Further investigations excluded the formation of new CO.

[Assessment of damage to the child in acute CO poisoning in pregnancy]. / Zur Bewertung der kindlichen Schädigung bei akuter CO-Vergiftung der graviden Frau.

Diaplacental transition of CO is discussed in two cases of lethal CO intoxication of pregnant women. Foetal CO-Hb has a time lag of several hours against maternal CO-Hb. In highly acute CO intoxications noxious foetal CO intoxication may not occur in spite of high maternal CO concentrations. However, there is a possibility of foetal hypoxia based on maternal hypoxaemia. In cases of subacute CO exposure for several hours, higher CO concentrations may be found in the foetal blood than in the maternal blood. Oxygen therapy of such CO intoxication cases must continue for a certain time after the mother had been detoxicated, because foetal CO elimination lags behind that of the mother. Subacute CO intoxications with sublethal CO-Hb concentrations may cause foetal damage and intra-uterine death as a consequence of CO-Hb, cellular toxic CO-effects and the hypoxia caused by maternal hypoxaemia. Medical decision for interruption of pregnancy as a consequence of foetal indication should be taken after due consideration of the legal problems involved in such action.

[Unusual course of myelography. Case report]. / Ungewöhnlicher Verlauf einer Myelographie. Kasuistischer Beitrag.

During performing a lumbar myelography the contrast medium, which was injected correctly, suddenly disappeared. By measuring the blood-iodine concentration a flow of contrasting medium into the venous system was found. This phenomenon may explain an acute allergic reaction.

[Detectability of poisons in paraffin-embedded organ parts]. / Zur Nachweisbarkeit von Giften in paraffineingebetteten Organteilen.

The detectability of metals and drugs in histological organ parts embedded in paraffin was tested in 24 cases, which had been analyzed before. The liver, kidney and brain parts were separated from the paraffin by heating the paraffin up to 110 degrees C and were homogenized by means of Ultra-Turrax blendor and ultrasound. Analysis was realized using gas chromatography, atomic absorption and mass spectrometry. Only 1.5%-4% of the original quantities of metals (As, Tl, Hg) was found in the embedded organs. Drugs could not be detected except for a low percentage of phenobarbital (2 cases) and bromine (3 cases). Reliable estimations cannot be made about the concentrations in the organs before the embedding procedure.

[Acute and subacute fetal CO-poisoning]. / Zur akuten und subakuten fötalen CO-Intoxikation.

The main principles of placental CO exchange in cases of CO intoxications of pregnant women are shown. Fetal COHb lags behind maternal COHb by several hours depending on the exposure pattern. During CO elimination the fetal COHb levels again lag behind the mother's. A case of a lethal CO intoxication of a pregnant woman, mens IX, with exposure time of 10-12 h and COHb of 75% for the mother and 46% for the fetus allows to make conclusions about process of intoxication and about different times of death for mother and fetus. In highly acute lethal intoxications of the mother COHb in fetal blood is low or negative. A vital danger of the fetus is not probable when mother survived a short CO exposure.

Reduced menstrual blood loss by release of an antifibrinolytic agent from intrauterine contraceptive devices.

Lippes Loop and Multiload intrauterine contraceptive devices (IUDs) were fitted with silicone rubber sleeves which either did not contain any compound (blank) or contained the antifibrinolytic agent, epsilon-aminocaproic acid (EACA. In vitro measurements showed that the antifibrinolytic agent was released from the sleeves for a period of 20 days. After insertion into women, the blank Lippes Loop IUDs and Multiload IUDs as well as copper-containing Multiload IUDs caused a significant increase in blood loss beginning with the first menstrual cycle after insertion. The enhanced blood loss was generally retained during subsequent menstrual cycles. By contrast, the menstrual blood loss induced by IUDs containing EACA sleeves was not significantly greater during the first menstrual cycle after insertion that the preinsertion levels. When no more EACA was released, menstrual blood loss increased to approximately the same level as that observed with the blank and copper IUDs. Thus, release of EACA from an IUD retains menstrual blood loss at approximately physiologic levels. These results encourage the development of IUDs that are capable of releasing antifirbrinolytic agents over a long period so that the antimenorrhagic effect is maintained.

PIP: Lippes Loop and Multiload IUDs were fitted with silicone rubber sleeves which either did not contain any compound (blank) or contained the antifibrinolytic agent (EACA), epsilon aminocaproic acid. In vitro measurements showed that the antifibrinolytic agent was released from the sleeves for a period of 20 days. After insertion into women, the blank Lippes loop IUDs and Multiload IUDs as well as copper-containing Multiload IUDs caused a significant increase in blood loss beginning with the 1st menstrual cycle after insertion. The enhanced blood loss was generally retained during subsequent menstrual cycles. By contrast, the menstrual blood loss induced by IUDs containing EACA sleeves was not significantly greater during the 1st menstrual cycle after insertion than the preinsertion levels. When no more EACA was released, menstrual blood loss increased to approximately the same level as that observed with the blank and copper IUDs. Thus, release of EACA from an IUD retains menstrual blood loss at approximately physiologic levels. These results encourage the development of IUDs that are capable of releasing antifibrinolytic agents over a long period so that the antimenorrhagic effect is maintained.

[Lethal intoxication by formalin during dialysis (author's transl)]. / Tödliche Formalin-Vergiftung bei Dialyse-Behandlung.

Systems for dialysis are disinfected, among other solutions, by formalin. Residues of formalin may remain in the interior of the system. A lethal intoxication with formalin by transvasal introduction of formalin during the dialysis of patients with nephritic disease cannot be observed very often. Two cases of death at the same time in one system for dialysis make evident that every case of death during dialysis should be investigated. The central symptom in both patients was dyspnea. It is probable that formalin affects the transportation and exchange of oxygen with lethal hemolysis.

[Administration of D-penicillamine instead of penicillin with fatal results: allergy of the delayed type with protracted shock as fatal complication of treatment with D-penicillamine for rheumatoid arthritis in a child (author's transl)]. / Folgenschwere Verwechslung von Penicillamin mit Penicillin. Allergie vom Spättyp mit protrahiertem Schock als tödliche Komplikation der Therapie mit D-Penicillamin bei rheumatoider Arthritis im Kindesalter.

Following one-week treatment with D-penicillamine for rheumatoid arthritis a seven-year-old girl died with the clinical features of protracted circulatory shock. Several doctors had mis-diagnosed the skin changes and mistakenly prescribed penicillamine, given for the rheumatoid arthritis, instead of plenicillin at the latter's dosage. By the administration of penicillamine a hypersensitivity reaction of the delayed type had been induced which ended fatally due to severe shock.

[The diagnostic significance of coagulated heart blood in cases of death by acute asphyxia (author's transl)]. / Zum diagnostischen Wert von "geronnenem" Herzblut bei akutem Erstickungstod.

In cases of death by asphyxia, such as strangulation, hanging, drowning, lack of oxygen, compression of the chest, and carbon monoxide poisoning, the frequency of the liquid and coagulated state of blood in the heart was examined. Coagulated blood in the right heart can be found in cases of strangulation, hanging, and drowning, if simultaneously an elevated blood alcohol was present. The diagnostic significance of this result is discussed.