No evidence for systolic or diastolic left ventricular dysfunction at rest in selected patients with long-term type I diabetes mellitus.

We assessed left ventricular systolic and diastolic function using pulsed-waved Doppler echocardiography in a selected group of 20 patients with insulin-dependent diabetes mellitus (IDDM) (mean age, 35 +/- 8 years; mean diabetes duration, 17 + 7 years). Our patients were free of autonomic neuropathy and major micro- or macrovascular complications and had no evidence of ischemic heart disease or hypertension. The results were compared with those of 20 age- and sex-matched control subjects. We found that left ventricular geometry and mass, systolic function by M-mode and 2D-echocardiography, isovolumetric relaxation time, deceleration time and the PEP/LVET ratio were not significantly different between patients and control subjects. Hemodynamic parameters were also not significantly different except for a slightly higher heart rate in the patient group (75 +/- 11 vs. 68 + 6 bpm, P = 0.019). After correction of A-peak velocities for differences in heart rate, there was no significant difference of Doppler indices of diastolic left ventricular function between patients and control subjects. The absence of significant left ventricular systolic and diastolic dysfunction by Doppler echocardiography in our study patients may be explained by our patient selection. Left ventricular dysfunction in diabetic patients without concomitant hypertensive or ischemic heart disease may only occur in conjunction with microvascular disease in other organ systems, with autonomic neuropathy or with poor metabolic control.

Morphological changes elicited in skeletal muscle by a Nd:YAG laser scalpel and electrocautery during surgical reduction of the human tongue.

A Nd:YAG laser scalpel was used for the surgical reduction of a human hyperplastic tongue. This instrument combines a fine cutting precision with haemostatic properties, whereby loss of blood is minimized and the surgeon's field of view unimpeded by flooding from the damaged capillary bed. The coagulative properties of Nd:YAG laser light are, however, insufficient to effect blood flow stasis in larger calibre vessels (arteries > 2 mm; veins > 3-5 mm), such as those located at the base of the tongue. For this purpose, bipolar diathermy (electrocautery) was employed. The ultrastructural changes incurred by skeletal muscle fibres using these two "heat" sources were compared. The damage profile elicited using each modality was similar: coagulation of myofilamentous proteins leads to destruction of fibrillar architecture with concomitant loss of periodic banding; on moving away from the wound margin, characteristic features are gradually restored. As the severity of these heat-induced effects decreases, there is a corresponding increase in superimposed dislocation and tearing phenomena induced by post-treatment swelling.

Devices for the control of laser transmission across the sclera during transscleral photocoagulation.

Improving the reproducibility of transscleral photocoagulation necessitates controlling the transmission of the laser beam through the sclera. Two factors make such control problematic: the locally increased transparency of the sclera resulting from the contact procedure and the occurrence of time-related relaxation phenomena. Two instruments have been devised to help control these factors. The first is a mechanical compensation unit comprised of magnets and a spring that allows the force exerted on the sclera to be adjusted to between 0.1 and 0.4 N, the pressure being determined by the outer diameter of the contact tip. The second instrument monitors the portion of the aiming beam reflected by the sclera as a means of determining the exact level of power actually transmitted through it. This information theoretically could be fed back to the treatment laser, allowing the level of power being delivered to be adjusted accordingly.

[Are there problems in changing diabetic patients from animal to human insulin?]. / Gibt es Probleme bei der Umstellung von Diabetikern von tierischem auf Humaninsulin?

In Switzerland it is still a debatable point whether diabetics whose treatment has been changed from animal to human insulin notice premonitory symptoms of hypoglycemia to a lesser degree and whether this could be hazardous for them. In a prospective study, 18 longstanding type 1 and type 2 diabetics, treated with insulin Lente MC, were selected and observed at frequent intervals for three months. This first period was followed by a transfer to human insulin (Protaphan HM) and a close observation for another three months. Before the transfer, all patients were well informed about a possible change in premonitory symptoms of hypoglycemia. The initial dose of Protaphan HM was 10% lower than in the treatment with Lente MC. During the three month period with human insulin, we observed no change with regard to blood-sugar regulation or Hb-A1. The most important observation was that the number of hypoglycemic episodes did not change after the transfer to human insulin. There were only mild to moderate degrees of hypoglycemia, the average being three episodes per patient. The change to human insulin was without any problems for the patients: they all preferred to stay on Protaphan HM for future treatment. Also, in general practice, patients can be changed without difficulties from animal to human insulin, provided that the above-mentioned precautions are respected.

Comparison of human and porcine insulin therapies in children with newly diagnosed diabetes mellitus.

A multicenter, longitudinal study of children below the age of 16 years with newly diagnosed Type 1 (insulin-dependent) diabetes treated either with porcine monocomponent insulin (n = 26) or semisynthetic human monocomponent insulin (n = 26) was performed during the first 24 months after onset of diabetes. The two groups were carefully matched for age, duration of disease symptoms, initial metabolic values, islet cell antibodies and HLA-DR antigens. During the 24-month observation period there was no significant difference between the two groups in respect to the clinical course, insulin dosage, HbA1 and residual B-cell activity. No child in either group had a real remission without necessitating insulin therapy. The prevalence of insulin antibodies increased slowly and was 62% in the group treated by human insulin and 52% in the porcine insulin-treated group after 24 months. The titres were generally low and there was no statistical difference between the two groups in respect to insulin antibody formation.

[Ultratard HM, a new human insulin. Advantages as compared to current preparations?]. / Ultratard HM, ein neues Humaninsulin. Vorteile gegenüber den bisherigen Präparaten?

Ultratard HM, a new human insulin, was studied in 10 patients with type II diabetes mellitus not previously treated with insulin. A control group consisted of 12 patients on Protaphane HM and 22 patients on Monotard MC. All patients tolerated the treatment well. After 6 months of therapy antiinsulin antibodies were detectable in only one patient on Ultratard HM. Therefore, in adult diabetics it is difficult to demonstrate a difference of antigenicity between human and porcine insulin. In another study blood glucose profiles were compared in 7 stable diabetics on Ultratard HM and Monotard HM. In our patients there was no significant difference in the activity profile of these 2 insulins.

A prospective study of the immunogenicity of porcine insulin in HLA-typed new insulin-treated diabetics.

Fifty-four diabetics were started on insulin therapy with highly purified porcine insulin (Velosulin, Insulatard, Mixtard) and treated for at least 1 yr with blood samples drawn at regular intervals for insulin antibody determinations. In 43 patients the insulin antibody response was correlated with HLA A, B, and DR antigens. Approximately half of the patients formed insulin antibodies within 6 months of treatment, and this incidence remained constant for up till 2 yr. In those patients who developed insulin antibodies a plateau of 12% insulin binding capacity was reached after 9-12 months which remained constant for up till 2 yr. Formation of antibodies to proinsulin and pancreatic polypeptide proved completely avoidable, and no local reactions at the injection sites were observed. There was indication of a positive association between HLA DR4 tissue types and the tendency to immune response to injected insulin (p = 0.07).

[Glucagonoma syndrome in a multihormonal pancreatic tumor]. / Glucagonomsyndrom bei einem multihormonalen Pankreastumor.

A 60-year-old patient developed signs and symptoms of glucagonoma syndrome (dermatitis, weight loss, anemia and hypoaminoacidemia). However, diabetes mellitus was absent. Glucagonoma was suspected because of markedly elevated plasma glucagon levels and the tumor was subsequently removed by surgery. Acidethanol extraction of the tumor and immunohistochemistry provided evidence of the presence of all four islet hormones, particularly that of glucagon and pancreatic polypeptide and to a lesser extent of somatostatin and insulin. Immunohistochemistry of the tumor (but not plasma) also showed the presence of alpha-HCG. Plasma glucagon immunoreactivity consisted to a large extent (approx. 90%) of a high molecular form of glucagon, probably proglucagon. In spite of the presence of alpha-HCG - which is assumed to be a marker of malignancy - the patient has been free of recurrence for the 2 1/2 years since surgery. The increasing number of cases reported during the past few years demonstrates that the syndrome is more common than previously suspected. Glucagon secretion and its typical clinical picture may be a valuable marker of a multihormonal pancreatic tumor. In a case of suspected glucagonoma, diagnosis can be established simply by obtaining a plasma glucagon level measurement.

Antipyretic activity of fluproquazone in man.

A multicentric, double-blind, randomized, parallel-group study was performed in patients with fever of diverse origin to test the tolerance and the antipyretic activity of single oral doses of 4-(p-fluorophenyl)-1-isopropyl-7-methyl-2(1H)-quinazolinone (fluproquazone) (200 mg, n = 18), acetylsalicylic acid (ASA) (1000 mg, n = 22) and placebo (n = 19). Whereas with placebo mean rectal temperature remained constant, a continuous fall was recorded with both active medications over the whole 3-h study period. With fluproquazone normalization of body temperature was nearly reached. Fluproquazone was more effective than placebo (p less than 0.001) and ASA (p less than 0.1), which in turn was more active than placebo (p less than 0.0001). No specific side-effects occurred.

[The antigenicity of various new chromatographically purified depot insulin preparations]. / Die Antigenität einiger neuer, chromatographisch gereinigter Depot-Insulin-Präparate.

Four groups of adult diabetics who had never received insulin before were treated for 10--12 months with the following insulin preparations: 1. Insulin Lente, purified by conventional methods; 2. Insulin Lente, purified by gel-filtration; 3. Insulin Lente Monocomponent (MC); 4. Insulin Monotard. Insulin antibodies were measured in these four groups at regular intervals and compared. MC Lente is significantly less antigenic than conventional Lente insulin, but Monotard, a pure pork insulin preparation, is even less antigenic than MC Lente (all 3 Lente preparations contain 70% ox insulin). The average insulin requirement in the Monotard group is significantly lower than in the conventional Lente group.

[Purity and antigenicity of the new insulin preparations]. / Reinheit und antigenität der neuen insulinpräparate

A short review on new types of insulin preparations purified by chromatography is presented. The purity of these new chromatographed insulins, which have almost completely replaced the conventional types of insulin, has been considerably improved. Our own investigations have revealed significantly lower antigenicity of porcine depot preparations compared with beef or mixed beef-pork insulins. By means of gel filtration and additional anion exchange chromatography the antigenicity of porcine insulin can be significantly reduced. Monocomponent insulins prepared by these methods produce low titers of insulin antibodies in only one third of diabetics treated by insulin for the first time. Mixed beef-pork Lente Insulin purified by single chromatography is also less antigenic than Lente Insulin of conventional purity, but more antigenic than pork insulin (e.g. Monotard). Pork insulin purified by chromatography is indicated in cases of insulin allergy, insulin resistance and lipoatrophy, and also for first insulin treatment in younger and middle-aged diabetics.