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1.
Ophthalmologe ; 111(3): 259-61, 2014 Mar.
Article in German | MEDLINE | ID: mdl-23774966

ABSTRACT

A 75-year-old man (not a contact lens wearer) presented with Fusarium-associated hypopyon keratitis. After several weeks of empirical and subsequently targeted antimycotic treatment, no considerable improvement was observed. However, after sclerokeratoplasty (11.2 × 11.2 mm) combined with prolonged antimycotic therapy a good local result with relapse-free long-term follow-up was achieved.


Subject(s)
Antifungal Agents/therapeutic use , Corneal Transplantation/methods , Fusariosis/microbiology , Fusariosis/therapy , Keratitis/microbiology , Keratitis/therapy , Scleroplasty/methods , Aged , Combined Modality Therapy , Drug Resistance, Multiple, Fungal , Fusariosis/diagnosis , Fusarium , Humans , Keratitis/diagnosis , Male , Treatment Outcome
2.
Neurology ; 76(17): 1463-71, 2011 Apr 26.
Article in English | MEDLINE | ID: mdl-21430296

ABSTRACT

OBJECTIVE: To evaluate the macroscopic and microscopic phenotype of the distal superficial temporal artery (STA) in patients with spontaneous cervical artery dissection (sCAD, n = 14). Arteries of accident victims, free of clinically apparent vascular disease, served as reference samples (n = 9). METHODS: Specimens of distal STA branches were obtained by biopsy or at autopsy. Their fine and ultrafine structure was documented by close-up photography of native STA branches, light microscopy, and electron microscopy in a case-control study. RESULTS: STA specimens from patients with sCAD revealed pathologic changes mainly in the adventitial and medial layers. In these areas, vacuolar degeneration and fissuring were associated with neoangiogenesis of capillaries and microscopic erythrocyte extravasation into the connective tissue. In addition, some specimens showed overt microhematomas close to the medial/adventitial border visible at low magnification. The reference arteries showed virtually no pathologic changes in the outer arterial layers. CONCLUSION: Bearing in mind that the STA is only a surrogate for the cervical arteries affected by sCAD, we propose the following pathogenetic model. We hypothesize that sCAD affects primarily the outer arterial layers. The process starts with degenerative changes at the medial-adventitial border associated with neoangiogenesis of capillary vessels branching from vasa vasorum in the adventitia. Leakage of neoangiogenetic capillaries releases blood cells into the connective tissue and leads to formation of microhematomas along the medial/adventitial border, as well as disintegration of the medial and adventitial texture. Microhematomas might then cause successive rupture of multiple neoangiogenetic capillaries and vasa vasorum, ultimately resulting in dissection.


Subject(s)
Arteries/pathology , Carotid Artery, Internal, Dissection/pathology , Connective Tissue/pathology , Vertebral Artery Dissection/pathology , Adolescent , Adult , Aged , Arteries/ultrastructure , Autopsy/methods , Biopsy/methods , Erythrocytes/pathology , Erythrocytes/ultrastructure , Female , Humans , Male , Middle Aged , Retrospective Studies , Rupture, Spontaneous/pathology , Young Adult
3.
Klin Monbl Augenheilkd ; 227(7): 564-7, 2010 Jul.
Article in German | MEDLINE | ID: mdl-20645229

ABSTRACT

The congenital dacryostenosis occurs frequently in about 5 % of all newborns. It may occur both as a unilateral and as a bilateral form with a family disposition for dacryostenosis. In a large number of cases we see a stenosis of the ductus nasolacrimalis due to a persistant membrane of Hasner or due to a mucosa plaque. The conservative treatment starts with lacrimal sac massage, detumescent eyes and nose drops. With further permanent complaints, probing of the lacrimal passages in a so-called "bundle wrap anaesthesia" may be performed depending on the age and physical appearance of the child. Further probing and silastic tube intubation under general anaesthesia should be performed in the case of persistence. Apart from the congenital stenosis we rarely find other alterations of the lacrimal system like aplasia of the canaliculi, saccus or ductus nasolacrimalis as well as tear duct diverticles or even fistula of the canaliculi or saccus which may lead to permanent epiphora. Facial disorders or dysmorphias with involvement of the lacrimal passages have to be accessed separately, with participation of various disciplines such as radiology, ear nose throat surgery, cranial-facial surgery and neurosurgery and therefore the patients need individual management and treatment.


Subject(s)
Dacryocystorhinostomy/methods , Lacrimal Duct Obstruction/congenital , Humans , Infant, Newborn
5.
J Neurol Neurosurg Psychiatry ; 79(9): 1007-12, 2008 Sep.
Article in English | MEDLINE | ID: mdl-18223019

ABSTRACT

BACKGROUND AND AIM: The aetiopathogenesis of spontaneous cervical artery dissection (sCAD) is largely unknown. Electron microscopic (EM) examination of skin biopsies of patients with sCAD revealed very subtle pathological changes of dermal connective tissue in about half of these patients leading to the hypothesis of an underlying connective tissue disorder. However, connective tissue abnormalities did not allow clear discrimination between patients and controls in our hands. Therefore, we sought to establish an objective basis for the assessment of connective tissue abnormalities in patients with sCAD using standardised morphometric assessment of collagen fibrils. METHODS: In this study a blinded examination was performed of collagen in skin biopsies and it sought parameters which are able to discriminate between patients with sCAD and controls. Various morphometric parameters were compared between patients with sCAD (n = 20) and control subjects (n = 18). RESULTS: Previously described "flower-like" collagen fibrils in skin biopsies were extremely rare in patients and controls and did not discriminate between the groups. However, they were abundant in the skin biopsy of a patient with Ehlers-Danlos syndrome type III (EDSIII) used as a reference. Morphometric parameters such as collagen fibril diameter, fibril density and relative fibril area did not discriminate between patients and controls on an individual basis, but the mean diameter of collagen fibrils in the skin was lower in patients with sCAD compared with controls while fibril density was higher resulting in nearly equal fibril areas per unit of area (relative fibril area) comparing both groups as well as individuals. CONCLUSIONS: Blinded pathological and morphometric analysis of collagen fibres in skin biopsies was, in our hands, unable to discriminate reliably between patients with sCAD and controls on an individual basis but did show differences in collagen fibril morphometry on a group basis. Furthermore, systematic and blinded pathological studies of skin biopsies in patients with sCAD and controls are needed.


Subject(s)
Fibril-Associated Collagens/metabolism , Skin/metabolism , Vertebral Artery Dissection/metabolism , Vertebral Artery Dissection/pathology , Adult , Biopsy , Diagnosis, Differential , Ehlers-Danlos Syndrome/diagnosis , Female , Humans , Male , Marfan Syndrome/diagnosis , Middle Aged , Skin/pathology
6.
Neurology ; 64(9): 1508-13, 2005 May 10.
Article in English | MEDLINE | ID: mdl-15883309

ABSTRACT

OBJECTIVE: To make an ultrastructural comparison of superficial temporal artery (STA) biopsy specimens from patients with spontaneous cervical artery dissection (sCAD) and controls. METHODS: The authors used light microscopic examination of semithin sections and electron microscopic examination of ultrathin sections of STA biopsy specimens from patients with sCAD and controls. RESULTS: STA biopsy specimens from patients with sCAD taken around the time of the dissection showed a zone of connective tissue weakening with fissuring at the junction between the tunica media (TM) and the tunica adventitia (TA) in seven of nine specimens and erythrocyte infiltration in eight of nine specimens but in none of the control specimens. Light microscopy demonstrated transparent circular spots that, on electron microscopy, turned out to represent erythrocytes and other cellular components at different stages of degradation. Occasionally, scattered immune cells were found in specimens from patients with sCAD. In addition, smooth muscle cells of the synthetic phenotype, some of them showing extensive vacuolation were more common in the TM of STA biopsy specimens from patients with sCAD than in control specimens. CONCLUSIONS: Signs of tissue weakening along the TM/TA junction in STA biopsy specimens of patients with sCAD but not in controls suggest the presence of a generalized arteriopathy leading to impairment of the stability of the arterial wall in patients with sCAD. Limiting factors of the study are that some control biopsies were obtained from autopsies and that the anticoagulation status of patients and controls were not completely comparable.


Subject(s)
Carotid Artery, Internal, Dissection/pathology , Temporal Arteries/pathology , Vertebral Artery Dissection/pathology , Adult , Biopsy , Carotid Artery, Internal, Dissection/physiopathology , Collagen/ultrastructure , Collagen Diseases/complications , Connective Tissue/pathology , Connective Tissue/physiopathology , Connective Tissue/ultrastructure , Erythrocytes/pathology , Erythrocytes/ultrastructure , Female , Genetic Predisposition to Disease/genetics , Humans , Male , Microscopy, Electron, Transmission , Middle Aged , Temporal Arteries/physiopathology , Temporal Arteries/ultrastructure , Tunica Media/pathology , Tunica Media/physiopathology , Tunica Media/ultrastructure , Vertebral Artery Dissection/physiopathology
7.
Child Care Health Dev ; 29(4): 281-90, 2003 Jul.
Article in English | MEDLINE | ID: mdl-12823333

ABSTRACT

BACKGROUND: Visual analogue scales (VAS) are used to assess the strength of perceptions of both children and adults in many clinical and research settings. Although the VAS has been shown by some authors to be reliable for use by children aged 5 years and older, others have proposed that young children, generally < or =7 years of age, may not have the conceptual ability to use a VAS. OBJECTIVE: To identify demographic and cognitive variables that would maximize the accuracy of predicting children's abilities to use a VAS. METHODS: Forty kindergarten children performed a seriation task, used a VAS to perform a calibration task and completed the Block Design and Vocabulary subtests of the Wechsler Preschool and Primary Scale of Intelligence-Revised (WPPSI-R). An estimated IQ was calculated from the WPPSI-R subtest scores. Socioeconomic status was assessed using the Hollingshead Four Factor Index of Social Status. Logistic regression was used to determine the best predictive models. Sensitivity, specificity, negative predictive value, positive predictive value and accuracy were calculated for statistically significant predictive models. MAIN OUTCOME MEASURE: Successful completion of the calibration study by the child. RESULTS: Only 42% of the subjects could use a VAS. The subject's age (> or =5.6 years), combined with estimated IQ (> or =100), was the best predictor of a child's ability to use a VAS (88% accuracy). CONCLUSION: The majority of kindergarten children in our study could not complete a VAS accurately. Cognitive ability, combined with chronological age, was the best predictor of a child's accurate use of a VAS, as determined by logistic regression. Paediatric researchers may need to consider alternative rating scales to measure perceptions in children under 7 years of age.


Subject(s)
Aptitude , Pain Measurement/psychology , Psychology, Child , Child , Child, Preschool , Cognition , Female , Humans , Intelligence , Male , Predictive Value of Tests , Sensitivity and Specificity
8.
Rofo ; 172(9): 764-9, 2000 Sep.
Article in German | MEDLINE | ID: mdl-11079090

ABSTRACT

PURPOSE: Small suspicious breast lesions that are only visible at MR imaging were preoperatively marked with a hook wire under MR-guidance to allow the removal of the lesion with tissue-sparing surgery. METHOD: In all patients the suspicious lesions were marked preoperatively under MR guidance with a hook wire using a commercially available stereotactic device. Interventions were performed with MR guidance on a 1.0 T and on a 1.5 T system. RESULTS: In 19 patients 22 lesions were localized. One lesion was missed and removed in a second procedure. The mean duration for localization was 66 +/- 20 min (range 38-119 min). In two patients two lesions were localized. The mean deviation of the wire tip to the lesion was 2.0 +/- 2.6 mm. In this series, 6 of 22 lesions were malignant. The mean diameter of the lesion was 7.6 +/- 2.6 mm (range 3-14 mm). CONCLUSION: Suspicious breast lesions detectable only in MR imaging can be accurately localized with a hook wire preoperatively under MR control to remove the lesion with a tissue-saving surgery.


Subject(s)
Breast Neoplasms/diagnosis , Magnetic Resonance Imaging , Radiology, Interventional , Adult , Aged , Biopsy , Breast/pathology , Breast Neoplasms/pathology , Breast Neoplasms/surgery , Female , Humans , Mastectomy, Segmental , Middle Aged , Sensitivity and Specificity
10.
J Bone Joint Surg Am ; 76(9): 1285-92, 1994 Sep.
Article in English | MEDLINE | ID: mdl-8077257

ABSTRACT

We studied twenty-five consecutive patients who had a closed tibial fracture to determine whether there was a relationship between compartment pressure and the distance at which the pressure was measured from the site of the fracture. Tissue pressure was measured in all four compartments of the leg at the level of the fracture and at five-centimeter increments proximal and distal to the fracture. The peak pressure was usually found at the level of the fracture and was always located within five centimeters of the fracture. The highest pressures were recorded in the anterior and the deep posterior compartments in twenty patients, including all five of those who had had a fasciotomy. The measured pressure decreased steadily when sampled at increasing distances proximal and distal to the site of the highest recorded pressure. Decreases of twenty millimeters of mercury (2.67 kilopascals) five centimeters adjacent to the site of the peak pressure were common. Compartment syndrome was diagnosed in five patients on the basis of clinical findings, and the diagnosis was confirmed when peak compartment pressures of more than the critical threshold (within twenty millimeters of mercury [2.67 kilopascals] of the diastolic blood pressure) were recorded. Three of these five patients had measured pressures that were less than the critical threshold within five centimeters of the site of the peak pressure. Failure to measure tissue pressure within a few centimeters of the zone of peak pressure may result in a serious underestimation of the maximum compartment pressure. Our results suggest that measurements should be performed in both the anterior and the deep posterior compartments at the level of the fracture as well as at locations proximal and distal to the zone of the fracture to determine reliably the location of the highest tissue pressure in a lower extremity when a compartment syndrome is suspected clinically. The highest pressure should be used in the decision-making process.


Subject(s)
Blood Pressure/physiology , Fractures, Closed/physiopathology , Muscles/blood supply , Tibial Fractures/physiopathology , Adult , Compartment Syndromes/etiology , Fractures, Closed/complications , Humans , Male , Tibial Fractures/complications
11.
Ophthalmologe ; 91(2): 244-50, 1994 Apr.
Article in German | MEDLINE | ID: mdl-8012145

ABSTRACT

Nine patients (11 eyes) with ocular cicatricial pemphigoid were treated with systemic azathioprine and a syngeneic nasal mucosa transplant from the inferior turbinate. Follow-up was 8-26 months (average 15 months). Grafting was successful in all cases. Treatment ameliorated the symptoms of pain in all patients and double vision in one. In 2 eyes in which simultaneous pannus resection had been performed, neither pannus nor corneal vascularization recurred. Late complications were recurrences with symblephara in two cases when azathioprine was stopped; in one patient with a serpiginous ulcer tectonic penetrating keratoplasty à chaud had to be performed; and in another a trophic ulcer was healed with a therapeutic contact lens.


Subject(s)
Azathioprine/administration & dosage , Conjunctivitis/surgery , Nasal Mucosa/transplantation , Pemphigoid, Benign Mucous Membrane/surgery , Aged , Aged, 80 and over , Combined Modality Therapy , Conjunctivitis/pathology , Female , Follow-Up Studies , Humans , Male , Middle Aged , Pemphigoid, Benign Mucous Membrane/pathology , Recurrence
12.
Refract Corneal Surg ; 9(2 Suppl): S85-90, 1993.
Article in English | MEDLINE | ID: mdl-8499387

ABSTRACT

We present our clinical strategy to treat corneal diseases with the excimer laser. Nine eyes with recurrent erosion after trauma, three eyes with band keratopathy, and one eye with secondary crystalline deposits and a leukoma adherens after perforating injury underwent excimer laser phototherapeutic keratectomy (PTK). The patients with recurrent erosion had at least six episodes in the 12 months, the other patients suffered from severe pain. The recurrent erosions were treated with 15 pulses (193 nm, 180 mJ/cm2, 10 Hz) after removing the epithelium. There was only one new episode within 6 months after treatment in a patient who failed to follow the postoperative therapeutic regimen. In the patients with band keratopathy we removed the calcium deposits mechanically and then used masking fluids to obtain a smooth surface. The crystalline deposits in the patient with leukoma adherens could be removed but recurred after 4 months; the patient still suffered from glare.


Subject(s)
Cornea/surgery , Corneal Diseases/surgery , Laser Therapy , Adolescent , Adult , Aged , Corneal Diseases/etiology , Corneal Diseases/physiopathology , Eye Injuries, Penetrating/complications , Female , Follow-Up Studies , Humans , Male , Middle Aged , Visual Acuity
13.
Klin Monbl Augenheilkd ; 202(2): 126-9, 1993 Feb.
Article in German | MEDLINE | ID: mdl-8487465

ABSTRACT

BACKGROUND: The authors report on the Phototherapeutic 193nm-Excimer Laser Keratectomy (PTK) for the treatment of superficial corneal opacities. MATERIAL AND METHOD: In two cases with corneal opacities after contact lens wearing and after therapy resistant keratoconjunctivitis epidemica respectively the treatment strategy is presented. The epithelium and the corneal opacities are removed mechanically as far as possible. Then the Excimer laser smoothing with masking fluids of different viscosity is performed. RESULTS: In both patients the visual acuity improved from 1/50 and 0.16 respectively to 0.7. Both eyes had an hyperopic shift. The patients were without pain within a follow-up period of 8 months after treatment. CONCLUSION: The phototherapeutical use of the 193nm Excimer laser to treat superficial corneal opacities can be regarded as a real alternative to conventional surgical techniques.


Subject(s)
Corneal Opacity/surgery , Laser Therapy/instrumentation , Adult , Cornea/pathology , Cornea/surgery , Corneal Opacity/diagnosis , Corneal Opacity/etiology , Female , Humans , Middle Aged , Postoperative Care , Refraction, Ocular , Visual Acuity/physiology , Wound Healing/physiology
14.
J Orthop Trauma ; 7(3): 199-210, 1993.
Article in English | MEDLINE | ID: mdl-8326422

ABSTRACT

Our objective was to define the critical tissue pressure at which irreversible muscle damage occurs and to compare our results to those thresholds advocated in the orthopaedic literature. A standard plasma infusion compartment syndrome model was created in a canine model. Four dogs were in each of four experimental groups with compartment pressure maintained as follows: (a) 30 mm Hg with support of diastolic blood pressure to a level > 50 mm Hg; (b) 20 mm Hg less than diastolic pressure; (c) 10 mm Hg less than diastolic blood pressure; (d) a level equal to the animal's diastolic blood pressure. All animals were sacrificed 14 days after the procedure. Histology revealed the following: (a) tissues pressurized to 30 mm Hg in a normotensive dog demonstrated no significant abnormalities; (b) tissues pressurized to 20 mm Hg less than diastolic revealed occasional cells undergoing regeneration but no evidence of infarction or fibrosis; (c) tissues pressurized to 10 mm Hg less than diastolic showed scattered small areas of infarction and fibrosis; and (d) tissues pressurized to diastolic blood pressure demonstrated more widespread infarction and scarring. The ischemic threshold of muscle, beyond which irreversible tissue damage occurs, is directly related to the difference in compartment and perfusion pressure. Our findings document this pressure to be 10 mm Hg less than diastolic blood pressure or within 30 mm Hg of mean arterial pressure. This data refutes the use of absolute tissue pressure values as a guide to the necessity of fasciotomy. To abort an impending compartment syndrome and avoid irreversible tissue injury and their sequelae, fasciotomy should be done if tissue pressure reaches within 10-20 mm Hg of diastolic pressure.


Subject(s)
Compartment Syndromes/pathology , Ischemia/pathology , Muscles/pathology , Animals , Compartment Syndromes/physiopathology , Disease Models, Animal , Dogs , Hindlimb , Microscopy, Electron , Muscles/ultrastructure , Pressure
15.
Am J Sports Med ; 20(3): 246-52, 1992.
Article in English | MEDLINE | ID: mdl-1636852

ABSTRACT

The GORE-TEX anterior cruciate ligament prosthesis has been implanted in 268 patients at our institution since April of 1984. Follow-up for this study was available on 70% of these patients (188). Eighty-one percent (152) of these had the ligament for chronic injuries, 14% (26) for acute, and 5% (10) for subacute injuries. The patient population had an average age of 27.6 years (SD = 8.4) and a Tegner activity score of 6.05 (SD = 1.53). Prior procedures had been performed on 56% (105) of the patients. Concomitant procedures were performed in 73% (137) and included iliotibial band tenodesis, partial meniscectomy, posterior oblique ligament advancement, or meniscal repair. Followup averaged 48 months (range, 24 to 68). Evaluation included a questionnaire, physical examination, radiographs, KT-1000 arthrometer testing, and an activity score. Results were graded as excellent, good, fair, and poor. Acceptable results (good and excellent) were obtained in 83 patients (44%). Fifty-eight patients (32%) were rated excellent and 25 (13%) were rated good. Unacceptable results (fair and poor) were obtained in 105 patients (56%). Twenty-five patients (13%) were rated fair and 80 (42%) were rated poor. Subjective improvement was indicated by 166 patients (88%). Activity levels postoperatively as rated by the Tegner Scale improved in 2 (1%), remained the same in 167 (89%), and decreased in 19 patients (10%). Effusions occurred in 63 patients (34%) and caused an unacceptable result in 22 (12%). Rupture occurred in 23 patients (12%). Loosening greater than 3 mm occurred in 64 patients (34%) and led to unacceptable results in 37 (20%). Infection occurred in 5 patients (2.7%).(ABSTRACT TRUNCATED AT 250 WORDS)


Subject(s)
Anterior Cruciate Ligament/surgery , Knee Prosthesis , Polytetrafluoroethylene , Acute Disease , Adolescent , Adult , Anterior Cruciate Ligament/diagnostic imaging , Anterior Cruciate Ligament Injuries , Biomechanical Phenomena , Chronic Disease , Female , Follow-Up Studies , Humans , Knee Injuries/rehabilitation , Knee Injuries/therapy , Male , Middle Aged , Prosthesis Failure , Prosthesis-Related Infections , Radiography
17.
J Trauma ; 27(9): 1051-4, 1987 Sep.
Article in English | MEDLINE | ID: mdl-3656468

ABSTRACT

With increasing frequency trauma surgeons are advocating early internal fixation in open fractures. The effect of the fixation devices on the infection rate in contaminated wounds remains a concern as our clinical experience in this area has been mixed. To study the effects of internal fixation on bone infections a 3.5-mm stainless steel screw was inserted into rabbit femurs and the wounds contaminated with Staphylococcus aureus. The controls had the screw hole drilled and taped but the screw was not inserted. Thirty of 49 rabbits receiving the screw subsequently became infected whereas 19 of 56 control animals developed an infection. The difference was significant at the 0.05 confidence level.


Subject(s)
Fracture Fixation, Internal/adverse effects , Fractures, Open/complications , Osteomyelitis/etiology , Staphylococcal Infections/etiology , Animals , Disease Models, Animal , Rabbits
18.
J Allergy Clin Immunol ; 70(6): 452-7, 1982 Dec.
Article in English | MEDLINE | ID: mdl-6128357

ABSTRACT

Previous studies have documented that leukocytes from atopic individuals show reduced cyclic AMP (cAMP) responsiveness to isoproterenol, histamine, and prostaglandin E1. We questioned whether this blunted response was due to rapid enzymic breakdown of cAMP. We measured cAMP-phosphodiesterase activity in mononuclear leukocytes of patients with atopic dermatitis and allergic rhinitis and noted consistent, significantly elevated levels. Kinetic studies showed differences in two of three leukocyte enzyme forms between normals and patients. Isolated lymphocytes from atopic dermatitis patients lacked a low Km phosphodiesterase form and showed an increase in the high Km, high-activity form seen in normal monocytes. The increased phosphodiesterase activity provides an explanation for the blunted cAMP responsiveness in atopic leukocytes and may reflect a basic biochemical characteristic relevant to abnormal immunocellular regulation in atopic disease.


Subject(s)
3',5'-Cyclic-AMP Phosphodiesterases/blood , Adrenergic beta-Antagonists/pharmacology , Dermatitis, Atopic/immunology , Leukocytes/enzymology , Adolescent , Adult , Alprostadil , Cyclic AMP/blood , Dermatitis, Contact/immunology , Dose-Response Relationship, Immunologic , Histamine/pharmacology , Humans , Isoproterenol/pharmacology , Kinetics , Lymphocytes/enzymology , Monocytes/enzymology , Prostaglandins E/pharmacology , Rhinitis, Allergic, Seasonal/immunology
19.
J Cyclic Nucleotide Res ; 8(4): 211-24, 1982.
Article in English | MEDLINE | ID: mdl-6300207

ABSTRACT

We have previously demonstrated heterologous desensitization of human mononuclear leukocytes (MNL) by incubation of low (e.g., 10(-6)M) concentrations of histamine, isoproterenol and prostaglandin E1. Subsequent exposure of the cells to stimulating (e.g., 10(-3) to 10(-5)M) concentrations of any one of the three agonists shows reduced cAMP responses. Possible mechanisms for the subnormal responsiveness include rapid degradation of cAMP. In this report we demonstrated time-dependent elevation of cAMP-phosphodiesterase (PDE) activity following agonist desensitization. The increased enzyme activity was accompanied by a mirror-image decrease in cAMP responsiveness. The effect was rapid and prolonged, with recovery time proportional to desensitization time. Cycloheximide failed to inhibit the increase of cAMP-PDE activity caused by short-term histamine exposure, but partially diminished the elevation as the result of chronic histamine desensitization. We observed three different kinetic forms of cAMP-PDE in MNL, designated as I, II and III, each with distinctive Km and Vmax. Histamine desensitization increased the activity of form II and drastically reduced that of form I. Also we observed a possible conversion of lymphocyte cAMP-PDE from form I to the form II more characteristic of monocytes. Agonist-induced increases in cAMP-PDE activity and changes in enzyme kinetic characteristics represent a potentially important mechanism of functional desensitization. This may have significant effects on biological regulation of cyclic nucleotides.


Subject(s)
3',5'-Cyclic-AMP Phosphodiesterases/metabolism , Neutrophils/enzymology , Alprostadil , Calcium/physiology , Cycloheximide/pharmacology , Histamine/pharmacology , Humans , In Vitro Techniques , Isoproterenol/pharmacology , Kinetics , Prostaglandins E/pharmacology , Time Factors
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