Evidence for a small anion-selective channel in the cell wall of Mycobacterium bovis BCG besides a wide cation-selective pore.

Two channels were observed in extracts of whole Mycobacterium bovis BCG cells using organic solvents and detergents. The channels derived from organic solvent treatment had a single-channel conductance of about 4.0 nS in 1 M KCl in lipid bilayer membranes with properties similar to those of the channels discovered previously in Mycobacterium smegmatis and Mycobacterium chelonae. The channel was in its open configuration only at low transmembrane potentials. At higher voltages it switched to closed states that were almost impermeable for ions. Lipid bilayer experiments in the presence of detergent extracts of whole cells revealed another channel with a single-channel conductance of only 780 pS in 1 M KCl. Our results indicate that the mycolic acid layer of M. bovis BCG contains two channels, one is cation-selective and its permeability properties can be finely controlled by cell wall asymmetry or potentials. The other one is anion-selective, has a rather small single-channel conductance and is voltage-insensitive. The concentration of channel-forming proteins in the cell wall seems to be small, which is in agreement with the low cell wall permeability for hydrophilic solutes.

Implications of disease management in the future of managed care.

Disease management holds the promise of profound improvement in the care presently delivered to sufferers of specific diseases and provides the potential for a marked reduction in both short- and long-term health care costs. It has created an excitement that has formed new partnerships, caused managed care organizations to alter their focus, and encouraged the pharmaceutical industry to spend its wealth of resources on the total well-being of the patient. The authors address the somewhat ambiguous definition of disease management and examine the essential elements required to successfully implement programs of this nature.

Blood glucose levels stimulating hypoglycemic counterregulation are related to chronic diabetes control.

Intensive insulin therapy is associated with an increased risk of hypoglycemia. To assess the effects of chronic glycemic control on hypoglycemic counterregulation, 21 type I diabetic patients underwent an intravenous insulin infusion of 40 mU/kg/hr for up to 180 min. Five patients had blood glucose levels which fell below 25 mg/dl or significant neurological symptoms ensured. These patients were considered to have inadequate hypoglycemic counterregulation. Of the 16 patients having successfully completed the test, blood glucose levels stabilized at 40 +/- 2 mg/dl after 109 +/- 8 min of insulin infusion, indicating adequate hypoglycemic counterregulation. The levels at which blood glucose stabilized were compared with previous metabolic control as assessed by hemoglobin Alc. A positive correlation (r = 0.57, p = 0.02) was found between the two parameters. It is concluded that (a) long term metabolic diabetes control may affect hypoglycemic counterregulatory mechanisms and (b) intensive insulin therapy may make diabetic patients more vulnerable to hypoglycemia by lowering the effective blood glucose concentration associated with hypoglycemic counterregulation.

Comparison of the safety and effectiveness of human and bovine long-acting insulins.

Since ultralente insulin pharmacokinetics suggest faster absorption by human insulin when compared with bovine insulin using the subcutaneous route, the safety and efficacy of human ultralente in the outpatient setting was evaluated. Twenty type I patients participated in a randomized study using a crossover design of four six-week phases: (a) one daily injection of human ultralente; (b) two daily injections of human ultralente; (c) one daily injection of bovine ultralente and (d) two daily injections of bovine ultralente. Pre-meal human regular insulin was used with ultralente insulins and comprised 39 +/- 2% of the total daily insulin dose. Total and ultralente daily insulin doses were lower with human ultralente insulin (51.3 +/- 3.0 total and 30.9 +/- 3.4 ultra lente u/day) when compared to bovine ultralente insulin (57.8 +/- 4.4 and 36.1 +/- 4.4 u/day, p less than 0.01), yet the metabolic control achieved was virtually identical during both phases: (hemoglobin Alc 8.6 +/- 0.2% human vs. 8.4 +/- 0.4 bovine, p = NS). The frequency of mild hypoglycemia was 3.0 +/- 0.5 events per week vs 2.0 +/- 0.3 (p = NS). No severe hypoglycemia occurred. There were no differences between blood glucose daily profiles, insulin doses, hemoglobin Alc (8.6 +/- 0.4% BID vs. 8.4 +/- 0.3% QD injections) and occurrence of hypoglycemia between the single and two-dose long-acting regimens. These data indicate that long-acting semi-synthetic human insulin (a) can be effectively used as a once daily injection, (b) may be more biologically active than bovine, and (c) can be associated with safe and effective diabetes control.

Reduction of severe hypoglycemic events in type I (insulin dependent) diabetic patients using continuous subcutaneous insulin infusion.

In order to evaluate the safety and effectiveness of insulin pump treatment and to establish criteria for its use, we retrospectively studied 45 patients from a referral university diabetes clinic who were treated with either intensive subcutaneous insulin injections or continuous subcutaneous insulin infusion. Hemoglobin A1C was 8.5 +/- 0.3% (SEM) before and 8.1 +/- 0.1% during continuous subcutaneous insulin infusion (p = NS), but rose to 10.0 +/- 0.2% at a 16-month post-study follow-up. The frequency of ketoacidosis was 0.17 events/year before and 0.20 during infusion pump use (p = NS) and declined to 0.10 at the follow-up (p = NS). Severe hypoglycemia was reduced from 2.73 events/year to 0.22 during continuous subcutaneous infusion treatment (p less than 0.001), and from 3.72-0.32 (p less than 0.001) in a subgroup of 23 patients who initiated insulin pump treatment because of frequent and severe hypoglycemic events during intensive insulin injection treatment. Insulin pump use, compared to intensive insulin injections in a non-research setting, (a) is equally effective for maintenance of near normal glycosylated hemoglobin levels, (b) need not result in increased ketoacidosis, and (c) is effective for reducing hypoglycemic events. Thus, insulin pump treatment can benefit larger and randomized studies are needed to confirm these results.

Cellular immune alterations associated with human insulin therapy.

To evaluate the immunogenicity of human insulin preparations, the treatment of 10 insulin-dependent diabetic patients was changed from purified porcine insulins to lente and regular semisynthetic human insulin (SSHI, N = 5) or NPH and regular biosynthetic human insulin (BHI, N = 5). Circulating levels of T lymphocyte subsets, in vitro responses of enriched mononuclear cells to mitogens and circulating insulin antibody measurements were performed before and during the 24 weeks of treatment. Insulin antibody levels did not change significantly in either human insulin treatment group. Circulating levels of Leu 1 and Leu 3 positive cells, identifying total and helper/inducer T lymphocyte populations respectively, and the Leu 3:Leu 2 (helper/inducer: suppressor/cytotoxic) T cell ration were all reduced (p less than 0.025) at eight weeks in the BHI treatment group. Cells identified with murine monoclonal antibody, Leu 7 defining a natural killer cell phenotype, were increased in the SSHI group at four weeks of study (p less than 0.05). There was a decreased pokeweed mitogen-induced proliferation of mononuclear cells in SSHI treated patients (p less than 0.01) at 12 weeks and both insulin treatment groups had increased responses to phytohemagglutinin (p less than 0.05) but not concanavalin A at 24 weeks. These data indicate that changes in the cellular immune system without associated changes in circulating anti-insulin antibody levels can be observed in patients whose treatment was changed from purified porcine to human insulin preparations. Thus, cellular immune responses may be more sensitive than humoral immune responses as indicators of immunological alterations to insulin preparations.

Total protein concentration in selectively collected secretions from the middle and inferior meatus of the nose.

To clarify the characteristics of nasal secretions, a method for collecting human nasal secretion was devised. Total protein concentration in selectively collected secretions from the nasal cavity was determined using biochemical techniques. Dry absorbent cotton was inserted in each middle and inferior meatus of the nasal cavity for 30 min, and put in a test tube with a plastic sieve for centrifugation. After centrifugation at 5,000 rpm for 20 min, 10 microliters were obtained to measure the protein concentration the nasal secretions was made using spectrophotometry. The amount of nasal secretion samples collected was 50 to 400 microliters per site. Nasal secretions collected from the right middle and inferior meatus contained 80 to 2,450 mg/dl and 260 to 3,270 mg/dl of protein, respectively, while those from the left middle and inferior meatus contained 80 to 2,200 mg/dl and 175 to 3,050 mg/dl, respectively. It was concluded that this new method was clinically useful for collecting nasal secretions, and it permitted selective collection from predetermined sites in the nasal cavity. The total protein concentration level of nasal secretions collected by this method was higher in the inferior meatus than in the middle meatus of the nose, with statistical significance.

[Differential arthrographic diagnosis of the painful shoulder joint]. / Arthrographische Differentialdiagnose des schmerzhaften Schultergelenkes.

60 arthrograms of the shoulder were explored under morphologic and pathologic-anatomic aspects. Differentiation was made between acute and chronic pain. The possible findings in leaking of the contrast material out of the joint capsule are shown and discussed. Signs are quoted of degeneration of soft tissue and bone. The findings in patients with rheumatoid arthritis and a history of shoulder dislocation are summarised. Distension of the joint capsule without shoulder dislocation is described. Filling of the periarticular lymphatics is mentioned in different cases.

[Diagnosis of glomus caroticum tumors with transvenous digital subtraction angiography]. / Diagnostik von Tumoren des Glomus caroticum mittels transvenöser DSA.

This paper demonstrates the diagnostic value of transvenous DSA in carotid body tumours. Angiographic results in 6 patients show that this method was of diagnostic significance in all cases; in 5 of 6 patients the angiographic diagnosis was confirmed by subsequent surgery. Transvenous DSA, the invasiveness of which is only minimal, is useful in outpatients for identifying obscure palpable tumours of the lateral neck. Unnecessary or even highly dangerous surgical diagnostic interventions can thus be prevented.

[Differential diagnosis of breast edema in the roentgen image]. / Zur Differentialdiagnose des Mammaödems im Röntgenbild.

Multiple benign and malign intra- and extramammary diseases may induce a symptomatic oedema of the breast. 10 similar roentgenograms, which show an oedematous imbibition of the mammary corpus, were selected from a total of 3452 radiographs of the breast. Patients with representative findings, due to different disorders, are presented as case reports: diffuse infiltrating carcinoma of the breast, lymphogranulomatosis, diffuse metastasizing contralateral carcinoma of the breast, thrombosis of v. subclavia/axillaris, and decompensated cardiac failure. The various aetiologies are discussed for differential diagnosis.

[Differential diagnosis of allergic and vasomotor rhinopathy. Value of individual diagnostic possibilities]. / Zur Differentialdiagnose der allergischen und vasomotorischen Rhinopathie. Wertigkeit der einzelnen Diagnostikmöglichkeiten.

History, examination, x-rays and blood tests are usually not very helpful in distinguishing between vasomotor and allergic rhinitis. The best methods are skin-tests and investigations which test the reaction of the nasal mucosa directly. Nasal provocation has so far been the best method of differentiating an allergic from non-allergic rhinitis. The estimation of IgE-concentration in nasal secretion is a promising new method. IgE values over 10 I.U. are found in persons with allergic rhinitis. The IgE-values are lower than 10 I.U. in more than 90% of non-allergic subjects. Estimation of IgE-concentration in nasal secretions seems to be as good as the nasal provocation test but easier.

[Diagnostic value of nasal secretions, current state: normal values. 1]. / Nasensekretdiagnostik, aktueller Stand: Normalwerte. Teil 1.

Separation of pure nasal secretions has been very difficult until now. Therefore, examinations were performed only with a small number of patients. Employing a new method to separate pure nasal secretions it is now possible to perform routine examinations. In this paper the protein composition and electrolyte patterns of normal human nasal secretion is reported. The amount of nasal secretion depends from the location and region of human nasal mucosa. The average amount is between 135 and 75 microliters. The protein concentration shows a very wide variation in the normal secretion between 200 and 3500 mg%. The average concentration in the upper nasal meatus is 950 mg%, in the lower nasal meatus 1100 mg%. Selective glycoprotein stainings show that the main part of nasal secret proteins are glycoproteins. The electrolyte concentrations were calculated for sodium 90-148 mval, potassium 6-28 mval and calcium 2-3.5 mval.