Heinz Drexel

Treatment of severe cancer pain by low-dose continuous subcutaneous morphine

&NA; In a prospective and intraindividually controlled trial, we have compared the efficacy and safety of a continuous subcutaneous morphine infusion with conventional intermittent oral or subcutaneous morphine application. Twenty‐eight in‐patients with cancer pain received a short‐term infusion lasting 2–42 days, and 8 out‐patients underwent long‐term infusion from 49 to 197 days during the terminal stage of their disease. Continuous subcutaneous morphine infusion significantly (P < 0.001) improved both pain and quality of life when compared to conventional morphine application. With continuous infusion, 5–48 mg (median 19 mg) of morphine was required daily, significantly (P < 0.001) less than the 10–90 mg (median 50 mg) necessary with conventional use. As a result of lower dosage, side effects under continuous infusion were infrequent and mild. Constipation occurred in 3 of the 36 patients and was always controlled by the addition of laxatives; no nausea, sedation or respiratory depression were observed. Signs of tolerance developed in 2 patients on long‐term infusion, but the use of continuous subcutaneous methadone for 2 weeks reversed the tolerance. The study presented indicates that low‐dose continuous subcutaneous morphine provides a valuable treatment modality for severe terminal cancer pain exhibiting a high degree of both efficacy and safety.

Myoglobinemia in the early phase of acute myocardial infarction

Close-meshed determinations of plasma myoglobin, creatine kinase, and its isoenzyme MB were carried out in nine patients admitted to the clinic less than 4 hours after the onset of symptoms in the course of acute myocardial infarction (AMI). Myoglobin clearly appears earlier (mean 2 hours and 30 minutes) in the plasma than creatine kinase (mean 4 hours and 15 minutes) and isoenzyme MB (mean 5 hours and 30 minutes after the onset of symptoms). During the first hours of AMI plasma myoglobin shows multiple peaks in all patients. Because this pattern is observed only with myoglobin but not with creatine kinase, it appears that myoglobin mirrors the early course of the necrosis more distinctly than creatine kinase. Plasma myoglobin was also found elevated after intramuscular injections and a high voltage accident. Myoglobinuria was not detectable after myocardial infarction.

Prevention of Perinatal Morbidity by Tight Metabolic Control in Gestational Diabetes Mellitus

In a prospective controlled trial, we studied the effect of tight metabolic control on the outcomes of 102 gestational diabetes mellitus (GDM) pregnancies compared with outcomes of 102 matched nondiabetic control pregnancies. Women with GDM were treated to achieve and maintain a blood glucose concentration of <130 mg/dl at 1 h after breakfast. Treatment consisted of a diet low in oligosaccharides and fat and, if necessary, once daily insulin. By the end of gestation, 88 of the 102 women with GDM received insulin at a mean dose of 18 U/day. Duration of insulin therapy ranged from 3 to 32 wk with a median of 11 wk. Perinatal outcome of GDM pregnancies under this management equaled that of control pregnancies. The full spectrum of excess morbidity from GDM was prevented, and normal distribution of birth weight and normal rates of macrosomia, dystrophy, hypoglycemia, hypocalcemia, hyperbilirubinemia, fetal acidosis, and low Apgar scores were achieved. No mortality was observed. In addition to the two main study groups, we also studied a third group of 24 women with GDM whose treatment lasted ≤5 wk due to late diagnosis. This suboptimally treated group demonstrated a significant (P < .05) increase of macrosomia and umbilical artery acidosis compared with the well-treated GDM group. The study reported herein demonstrates that excess mortality and morbidity typically observed in GDM can be prevented by early institution of tight metabolic control, which required insulin in 86% of our patients.

Low Sensitivity of Serum Fructosamine as a Screening Parameter for Gestational Diabetes Mellitus

Oral glucose tolerance testing (OGTT) and quantification of serum fructosamine levels were performed in 190 asymptomatic women in weeks 24-28 of pregnancy. OGTT identified 10 of the 190 women as having gestational diabetes, but serum fructosamine quantification failed to do so because none of these 10 women exhibited levels exceeding the normal limit of 2.76 mmol/l. The mean fructosamine level in this group was 1.72 +/- 0.25 mmol/l compared to 1.60 +/- 0.15 mmol/l in the other 180 women without gestational diabetes. Fructosamine was found to correlate only with postload glucose values in excess of 180 mg/dl at 2 h (r = 0.87; p = 0.01), i.e. with the highest overall glucose values, but not with fasting glucose or milder postprandial hyperglycemia of under 180 mg/dl. We conclude that quantification of fructosamine detects only the rather severe cases of gestational hyperglycemia, but is too insensitive to uncover mild asymptomatic gestational diabetes mellitus, and we do not consider fructosamine to be a useful parameter for the diagnosis of this condition.

Post-heparin lipolytic activities and alterations of the chemical composition of high density lipoproteins in alcohol-induced type V hyperlipidemia.

In order to study the effects of chronic alcoholism, 3 groups of patients were investigated and compared to 10 healthy controls. Group I consisted of 9 heavy drinkers, who exhibited type V hyperlipidemia (HLP) under alcohol intake. Group II consisted of 7 patients, who previously had type V HLP under the influence of alcohol. At the time of the investigation, however, they had ceased alcohol drinking for at least 6 months and were normolipidemic. Group III consisted of 7 heavy drinkers without hyperlipidemia. Compared to controls, group I had significantly decreased plasma concentrations of high density lipoproteins2 (HDL2) and HDL3 (both P less than 0.01); activities of post-heparin lipoprotein lipase (LPL) and hepatic lipase (HTGL) as well were excessively decreased (both P less than 0.01). In group III LPL was also decreased (P less than 0.01), but HTGL was distinctly (P less than 0.01) higher than in controls. No such differences could be demonstrated for the patients of group II. Acute alcohol withdrawal from a patient suffering from alcoholism with HLP led to a sharp increase of LPL with a simultaneous decrease of VLDL within 2 days and a more delayed increase of LDL, HDL2 and HTGL, all reaching normal values within 12 days after cessation of alcohol drinking. With respect to the apolipoprotein (apo) composition of HDL2, patients of group I and group III exhibited a significantly lower percentual content of apo C-I at the expense of a significantly higher content of apo A-II as compared to controls and patients of group II. In group I and II, the percentual content of apo D in HDL2 was significantly higher than in controls and in group III. It is concluded that severe alcohol intake strongly impairs LPL in patients with HLP. The pronounced increase of HTGL in some patients (group III) may protect these individuals from HLP. The increased content of apo D in HDL2 may be a possible primary trait for alcohol-inducible HLP.