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K Wahl

Publications and source records attributed to K Wahl.

13 recordsLinked to original sources

A new understanding of attention-deficit disorders--beyond the age-at-onset criterion of DSM-IV.

For decades, ADHD has been seen primarily as a behavior disorder affecting only young children, primarily boys, causing them to be inattentive and disruptive in school. Research has now established that ADHD affects females as well as males, and that impairing symptoms, for most, persist into adulthood. It has also been shown that this disorder impacts many aspects of life that extend well beyond problems in school. This disorder impairs not only one's ability to sit still and listen, but also the capacity to organize tasks and materials, to sustain effort on tasks, and to utilize short-term memory for daily activities. Studies of children, adolescents, and adults with ADHD indicate that many suffer from a variety of cognitive impairments that extend beyond symptoms listed in the DSM-IV diagnostic criteria for ADHD. These include chronic problems in regulating alertness, in reading comprehension, and in modulating emotions, that occur more frequently in persons with ADHD than in the general population. This article describes recent research findings demonstrating the wide range of cognitive impairments associated with ADHD, which are related to a new model of ADHD, such as developmental impairment of executive functions of the brain.

Adolescent↗

Neutralizing increases discomfort associated with obsessional thoughts: an experimental study with obsessional patients.

Cognitive-behavioral theories suggest that the development of neutralizing is crucial in the development and persistence of obsessional problems (OCD). Twenty-nine patients with a Diagnostic and Statistical Manual of Mental Disorders (4th ed., American Psychiatric Association, 1994) diagnosis of OCD were randomly allocated to 2 conditions. Both listened to repeated recorded presentations of their intrusive thoughts and either neutralized (experimental group) or distracted themselves (control). Discomfort was rated during this 1st phase and then during a 2nd phase without neutralizing or distraction. The experimental group showed a similar level of discomfort in the 1st phase, which significantly reduced during the period compared with controls. The experimental group experienced significantly more discomfort during the 2nd phase, and significantly stronger urges to neutralize and distract at the end of this phase than controls.

Adult↗

Cellular profile of cytokine production in a patient with visceral leishmaniasis: gammadelta+ T cells express both type 1 cytokines and interleukin-10.

The cytokine profile of CD4+, CD8+ T cells, gammadelta+ T cells and natural killer (NK) cells (CD94+CD3-) was studied in a patient with visceral leishmaniasis (VL). The otherwise healthy, human immunodeficiency virus-negative patient acquired the disease in Tuscany, Italy. Diagnosis was made by demonstration of high concentrations of antibodies against Leishmania antigens in serum. Flow cytometry for the detection of intracellular interferon-gamma (IFN-gamma), interleukin (IL)-2, IL-4, IL-6, IL-10, IL-13 and tumour necrosis factor (TNF)-alpha expression in peripheral blood mononuclear cells stimulated with phorbol 12-myristate 13-acetate and ionomycin was performed, followed by treatment with liposomal amphotericin B. CD4+ cells were identified as major cytokine-expressing cells, capable of producing both type 1 and type 2 cytokines. A high frequency of IL-4- and IL-13-expressing CD8+ cells was noted. NK cells and gammadelta+ T cells, thought to be involved in innate host defences against Leishmania, expressed IFN-gamma and TNF-alpha. Ten per cent of gammadelta+ T cells expressed IL-10, predominantly together with IFN-gamma, suggesting additional immune-regulatory roles for this T-cell subset in VL.

Amphotericin B↗

Immunological tolerance to inhaled antigen.

Regulatory mechanisms exist in the immune system to limit the induction of pathogenic responses to antigens encountered within the respiratory tract. The development of allergic disease is thought to arise as a result of the breakdown in these regulatory processes. In this review we examine the nature of immune responses generated to inhaled protein antigens and the mechanisms used to establish tolerance to inhaled antigens.

Antigens↗

Mental rotation, memory scanning, and the central bottleneck.

Two reaction-time experiments using the psychological refractory period paradigm examined whether two prominent tasks, i.e., mental rotation and memory scanning, require access to a single-channel mechanism and must therefore be performed sequentially with other operations requiring the same mechanism. On each trial, subjects made speeded responses to a tone (Exp. 1) or a character (Exp. 2, with symbolic SR-compatibility of the character manipulated) as Task 1 and to a letter (for blocks with mental rotation) or a digit (for blocks with memory scanning) as Task 2. The set-size effect was constant across SOAs, suggesting that memory scanning cannot be performed in parallel with response selection of Task 1. The effect of orientation, however, decreased with decreasing SOA. The decrease was even intensified if Task 1 bottleneck processes were prolonged by symbolic SR-compatibility. The exact pattern of underadditivity, however, was not predicted by current theories of dual-task performance. The results contradict a central bottleneck model but are in line with extensions of the model proposed by Meyer and Kieras.

Female↗

Kinetics of biosynthetic human proinsulin in patients with terminal renal insufficiency.

Eight volunteers with terminal renal insufficiency having consented to the investigation, were given an i.v. bolus administration of 40 pmol biosynthetic human proinsulin on their dialysis-free day. Intravenous blood for the determination of blood glucose proinsulin, insulin and C-peptide was collected in short intervals for 6 hours and thereafter in longer intervals for 24 hours. Proinsulin was determined by immunoradiometric assay with monoclonal antibodies. The proinsulin kinetics were compared with the kinetics of normal volunteers. The behaviour of proinsulin concentration-time is best described with a 3-compartment model. The dominant biological half-life in terminal renal insufficiency was 6.8 hours which signifies a 4.4-fold increase of the normal half-life. The distribution volumes (V1) in the central compartment do not differ in the two groups, whereas the distribution volume after complete distribution (Vss) is significantly increased in renal insufficiency. The total metabolic clearance in renal insufficiency namely 0.63 ml/kg/min is 2.6 times lower compared to normal subjects with 1.67 ml/kg/min. The extra-renal clearance is 39% of the total metabolic clearance rate, whereas the renal clearance comprises 61%. Peripheral conversion from proinsulin to insulin and C-peptide does not occur in terminal renal insufficiency. The basal endogenous proinsulin secretion rate in renal insufficiency does not differ from that of normal volunteers. The following conclusions can be drawn: 1) Hyperinsulinism observed in renal insufficiency can be explained by circulating proinsulin. 2) In the potential therapeutic use of biosynthetic human proinsulin in diabetics with renal insufficiency dosis adjustment according to the remaining renal function would probably be required.

Adult↗

Action profile of biosynthetic human proinsulin trials with the BIOSTATOR in metabolically normal subjects.

Studies to examine the pharmacokinetics and pharmacodynamic properties of biosynthetic human proinsulin were conducted with the aid of the "glucose-controlled insulin infusion system BIOSTATOR". Seven metabolically normal healthy volunteers were given subcutaneous injections of 0.1 mg human proinsulin per kg body weight, and the subsequent behaviour of the serum proinsulin concentration was monitored over a period of 21 hours. The drop in the blood-sugar levels was counteracted by corresponding infusions of glucose by the BIOSTATOR via a special clamp technique. The intensity and frequency of the glucose infusions given by the BIOSTATOR equipment enable us to draw conclusions regarding the hypoglycaemic efficacy of human proinsulin. Two to three hours after the subcutaneous injection, the serum proinsulin concentration had reached its plateau-like maximum value. After approximately 5 hours it had dropped to 2/3 of the maximum, and after another 3 to 4 hours it had fallen further to 1/3 of the maximum. It returned virtually to its initial value after a total of 14 to 16 hours. The dextrose infusion rate calculated by the BIOSTATOR reflects these changes in the form of an "action profile". Proinsulin has a mean transit time (MTT) of 322 minutes. This is longer than the MTT of normal insulin (188 minutes) but markedly shorter than that of NPH insulin (625 minutes). If the hypoglycaemic effects of insulin and human proinsulin are compared on the basis of the areas under their respective action profile curves, the hypoglycaemic effect of 1 mg human proinsulin corresponds to 5.2 IU insulin.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Pharmacokinetics of biosynthetic human proinsulin following intravenous and subcutaneous administration in metabolically healthy volunteers.

40 pmol of biosynthetic human proinsulin was administered to 8 healthy volunteers by intravenous and by subcutaneous route. Following proinsulin administration, venous blood was collected in regular intervals within which proinsulin was determined by a specific radioimmunometric assay with monoclonal antibodies. The proinsulin concentration was determined simultaneously with the insulin and C-peptide radioimmunoassay. Through this investigation the following kinetic parameters were found: The kinetics of the biosynthetic human proinsulin can be best described by the 3-compartment model. The dominant biological half-life was 92 minutes. In intravenous proinsulin administration a proinsulin mean transit time of 80 minutes was found, whereas in subcutaneous administration a proinsulin retention time of 225 minutes was measured. The mean resorption velocity of the subcutaneously applied proinsulin amounted to 145 minutes. Two lag times for subcutaneous resorption can be described, a short one with 9.4 minutes and a long one with 65 minutes. The initial distribution volume for proinsulin was 3.8 l, whereas the distribution volume after complete distribution was 9.3 l. The mean total metabolic clearance was determined with 120 ml/min. Since no difference for the proinsulin concentration was found using the 3 different determination methods a peripheral proinsulin conversion to insulin and C-peptide is not likely. The basal endogenous secretion rate for proinsulin is 68.7 pmol per hour.

Adult↗

[Pharmacokinetics of insulin administered intraperitoneal in a bolus form (author's transl)].

Although carbohydrate-intake and subcutaneous insulin injection in the insulin dependent diabetics are brought to match with one another, there is often an incongruity between the momentary insulin need and the actual insulin supply, because insulin is resorbed relatively slow from the subcutaneous injection site. While the plasma insulin concentration in healthy persons after carbohydrate-intake reaches its maximum after ca. 45 min, the maximum insulin concentration after subcutaneous application of regular insulin is observed only after ca. 2 h. For this reason, we studied whether a faster rise in the insulin concentration can be obtained by intraperitoneal bolus application of insulin. 5 metabolic healthy volunteers received 20 UI regular insulin diluted in isotonic saline solution injected intraperitoneal. The insulin concentration in the peripherovenous system was examined. In order to prevent severe hypoglycaemia the test persons were connected to a Biostator (so-called artificial Beta-cell), which delivered glucose automatically when the blood glucose concentration fell below the 60 mg/dl - level, and thus avoided a drastic fall of the blood glucose. A rapid increase in the plasma insulin concentration was observed within a few minutes after the intraperitoneal bolus injection of insulin. After ca. 20 min the maximal insulin concentration was reached. Already after ca. 2 h the plasma insulin levels fell off and approached the initial values. Consequently, the changes of insulin concentration after intraperitoneal bolus application of insulin correspond widely to the insulin curve characteristic of metabolic healthy persons after carbohydrate-intake. Thus, the intraperitoneal bolus injection of insulin presents a mode of application, which must be pursued further in the treatment of insulin dependent diabetics.

Adult↗

Innervated temporal-muscle mastoid flaps.

Histological comparisons have been made of predicted temporal-muscle flaps with and without an intact nerve supply. The viability of the musculoplasty depends on maintenance of the neural bundle.

Animals↗

Pharmacokinetics of biosynthetic human insulin and characteristics of its effect.

In the last 2 years we have developed a new method for determining insulin biologic activity with the help of the glucose-controlled insulin infusion system (GCIIS). Primarily this closed-loop system infuses insulin. But to prevent hypoglycemia, it can in addition, infuse glucose below a certain blood glucose minimum. This effect is used to reproduce insulin biologic activity. After subcutaneous injection of the insulin to be tested in healthy persons (not in insulin-dependent diabetic subjects), the blood glucose level falls, and this is checked by the counterregulatory glucose delivery from the apparatus. The time and intensity of glucose delivery from the GCIIS reflect the insulin effect, so that each insulin manifests its own particular biologic activity.

Animals↗

Insulin concentrations and time-action profiles of three different intermediate-acting insulin preparations in nondiabetic volunteers under glucose-controlled glucose infusion technique.

This study describes the pharmacokinetics of three intermediate-acting insulin preparations, NPH porcine insulin, NPH human insulin (recombinant DNA), and "Depot-A" insulin, a mixture of 20% regular and 80% NPH human insulin from Eli Lilly and Company. Metabolic healthy normal weight volunteers were selected for the study. After overnight fasting, each test person received 0.4 U of each insulin per kg body weight injected subcutaneously in the triceps area of the arm. To prevent severe hypoglycemia, the test persons were connected to a "GCIIS Biostator" with blood glucose clamp at the 60 mg/dl level. Peripheral blood was sampled at regular intervals for glucose, insulin, and C-peptide determination. More elevated insulin levels were measured after application of both NPH human insulin and "Depot-A" insulin than after NPH porcine insulin. A more rapid decrease in the blood glucose concentration was observed after injection of both human insulin preparations than after porcine insulin. The dextrose output of the "GCIIS Biostator" was more pronounced in both human insulins than after the porcine preparation. After the injection of NPH human and NPH porcine insulin, significant differences were calculated between the concentrations of these two insulins in the blood, from the 2nd to the 10th hour (P less than 0.05-P less than 0.005) and between the dextrose output of the "GCIIS Biostator" from the 3rd to the 8.5th hour (P less than 0.05). The fall of the C-peptide concentration to the lower detection limit of the assay reflects suppression of the endogenous B-cell secretion and confirms the measure of peripheral insulin concentrations as a result of the exogenously applied insulin. Although all investigations were performed under identical experimental conditions and equal dosages of each insulin were injected, higher insulin concentrations and a stronger biologic effect, shown by larger amount of dextrose delivered, were observed in both human insulins than in porcine insulin. Why this phenomenon occurs is as yet unclear. The clamp technique used with the "GCIIS Biostator" enables establishment of the biologic profile of any insulin, and thus represents a valuable tool in comparative studies.

Adult↗