Medical Literature - 1991

Alpha 2-macroglobulin-kallikrein complexes detect contact system activation in hereditary angioedema and human sepsis

Kaufman N, Page JD, Pixley RA, Schein R, Schmaier AH, Colman RW 6/1991 Blood

Activation of the contact system has been documented in severe sepsis and hereditary angioedema, but a sensitive, specific, and quantitative assay for assessing the degree of involvement of this proteolytic enzyme cascade is not yet available. We have developed a quantitative sandwich enzyme-linked immunosorbent assay (ELISA) for the alpha 2-macroglobulin-kallikrein (alpha 2M-Kal) complex using an F(ab’)2 derivative of a monospecific polyclonal antibody against alpha 2 M as the capture antibody and a unique murine monoclonal antibody, 13G11, against the heavy chain of kallikrein as the detector antibody. The assay does not detect complexes in normal plasma but reacts with complexes generated by activating normal plasma with dextran sulfate at 4 degrees C in a range of 5 to 375 nmol/L. A close correlation of the ELISA with an amidolytic assay for alpha 2M-Kal was documented. Patients with sepsis syndrome but negative bacterial blood cultures did not show elevated plasma complexes, whereas a majority of those with positive blood cultures did show modest elevation and a single patient with septic shock showed a very high level of alpha 2M-Kal complex. Similarly, a patient with classic hereditary angioedema (HAE) showed increased concentration of complexes on three separate occasions during attacks but normal levels between attacks. Two other HAE patients did not show elevated levels at quiescent periods. The ELISA for alpha 2M-Kal appears to be sensitive, specific, and quantitative, and it can be used to reflect the degree of contact system activation in human sepsis and in HAE attacks.

Jun 15;77(12):2660-2667

Available online at:

Anesthesia for athletes using performance-enhancing drugs

Joyce JA 4/1991 American Association of Nurse Anesthetists (AANA J)

Anabolic-androgenic steroids are used in the treatment of numerous medical conditions, including Fanconi’s anemia, hypogonadism, hereditary angioedema, hypopituitarism and impotence. However, because of their potent anabolic properties, athletes began to use them to enhance body strength, size and endurance. Despite warnings from the medical and scientific communities of dangerous side effects such as Wilm’s tumor, hepatocellular carcinoma, stroke and myocardial infarction, some athletes continue to use anabolic steroids. Among the numerous research publications, only one case report was found which related difficulties in anesthesia administration. This paper presents the physiologic changes associated with anabolic steroid ingestion and applies these changes to the administration of anesthesia.


Not available online.

C1-INH defect as an example of deficiency disease

Madalinski K, Sabbouh K, Chorazykiewicz M, Gregorek H 4/1991 Immunological Investigations: A Journal of Molecular and Cellular Immunology (Immunol.Invest.)

Primary defect of C1-inhibitor (C1-INH), the regulatory protein of the initial classical pathway of complement, is the cause of hereditary angioedema. Clinical symptoms involve potentially fatal obstruction of the upper respiratory tract, abdominal pains, and subcutaneous edemas. Since the description of functional tests for C1-INH two types of hereditary defect have been known: type I and type II. Sixteen patients with the type I of hereditary angioedema were diagnosed and treated in our hospital. The onset of the disease occurred between 1.5-12 y. of age. Clinical symptoms were observed in skin, gastrointestinal and respiratory tracts. Mean concentration of C1-INH in sera of 16 patients was 3.25 mg/dl, below 8.75 mg/dl that is the critical for well-functioning C1-INH. Inhibitory activity of C1-INH for C1 esterase in plasma was zero in most of the patients, while it was 0.94 +/- 0.20 U/ml in plasma samples of 91 healthy blood donors. Three modalities of treatment are available: substitution with C1-INH concentrate in acute attacks and antifibrinolytic and/or anabolic drugs for prophylaxis. We have obtained good therapeutic results with epsilon-aminocaproic acid (antifibrinolytic), 2g daily during 3 months, with 6 months intervals.


Available online at: (small fee)

Idiopathic gastric acid hypersecretion: treatment implications for refractory acid/peptic disorders

Lewis JH /1991 Alimentary Pharmacology and Therapeutics (Aliment.Pharmacol.Ther.)

Although in most patients with duodenal ulcer disease the ulcer heals after 8 weeks of treatment with standard doses of H2 blockers or other agents, in about 10% the ulcer does not heal. These patients are considered ‘refractory’ to treatment. Reasons often cited for non-healing include poor patient compliance, cigarette smoking, and non-steroidal anti-inflammatory drug (NSAID) use. Gastric acid hypersecretion also appears to be an important factor in non-healing with standard doses of antisecretory agents. We have defined idiopathic gastric acid hypersecretion as a basal acid output of greater than 10 mmol/h in the absence of an elevated fasting serum gastrin level (or a negative secretin test if gastrin level greater than 100 pg/ml) to exclude persons with Zollinger-Ellison syndrome. Among the acid/peptic-related disorders in which idiopathic gastric acid hypersecretion should be considered are refractory duodenal ulcer, refractory gastro-oesophageal reflux disease (especially patients with oesophagitis), postbleeding duodenal ulcer, and certain rare disorders such as hereditary angioedema. Some children with atypical abdominal pain may also be hypersecretors of gastric acid. Once identified, patients with refractory duodenal ulcer or gastro-oesophageal reflux disease are treated with incremental doses of ranitidine titrated against the level of gastric acid secretion that remains during therapy. Ranitidine was selected to avoid the dose-related antiandrogenic effects and potential hepatic cytochrome P450 system-related drug interactions that may occur with cimetidine. In most cases of refractory duodenal ulcer, doubling the standard dose of ranitidine (to 300 mg b.d.) is sufficient to achieve symptomatic relief and mucosal healing. Higher doses appear to be necessary for refractory oesophagitis. To date, no side effects have been associated with high doses of ranitidine (up to 1800 mg/day) for periods of longer than 6 months. Idiopathic gastric acid hypersecretion is an important factor in explaining why not all patients respond to a ‘standard’ ulcer-healing dose of H2 blocker, and it provides a rationale for use of higher-dose therapy as a safe and effective alternative to omeprazole or to combination drug therapy in refractory acid/peptic disease.

5(Suppl 1):15-24

Available online at: (small fee)

Long-term treatment of hereditary angioedema with attenuated androgens: a survey of a 13-year experience

Cicardi M, Bergamaschini L, Cugno M, Hack E, Agostoni G, Agostoni A 4/1991 Journal of Allergy & Clinical Immunology

Fifty-six patients affected with hereditary angioedema have been followed during long-term prophylaxis with attenuated androgens. The treatment was started in patients who had one or more severe attacks per month. In 24 patients, the therapy lasted for more than 5 years. The minimal effective dose usually did not exceed 2 mg/day of stanozolol or 200 mg/day of danazol. Only in two patients were these doses not sufficient to achieve the complete disappearance of symptoms. Irregular menstruation, but rarely amenorrhea, was the only significant side effect. One patient had to stop the therapy because of laboratory signs of hepatic cell necrosis. In one patient, danazol was administered during the last 8 weeks of pregnancy without side effects for the mother but with transient signs of virilization for the female baby. To find a biochemical marker for the minimal effective dose of androgen derivatives, we measured the plasma levels of C1 C1 INH complexes at different doses of stanozolol in four patients with hereditary angioedema. We found that these complexes, elevated before treatment, promptly reverted to normal values during androgen therapy and remained normal with any reduction of the dose of the drug as long as the patient remained symptom free. Therefore, the measurement of C1 C1 INH complexes appears to reflect the activity of the disease and not the amount of androgen that is administered.


Available online at:

Oral manifestations and dental management of patients with hereditary angioedema

Atkinson JC, Frank MM 3/1991 Journal of Oral Pathology & Medicine

Hereditary angioedema (HAE) is a genetic disorder in which affected individuals develop extensive, spontaneous angioedema of the extremities, gastrointestinal tract, and oropharynx. Dental treatment of unmedicated patients with HAE can trigger life-threatening pharyngeal edema. Previously, it was demonstrated that the administration of fresh frozen plasma (FFP) before surgery prevented angioedema attacks in 6 patients undergoing dental extractions. The present study examines the long term effectiveness of FFP in preventing angioedema from developing in 53 patients with HAE undergoing all types of dental treatment over a ten-year period. Only 3 of 45 patients (6.7%) covered with FFP had a minor angioedema attack after dental therapy in 10 yr. No attacks of moderate or severe swelling were seen. Attacks occurred independently of the disease activity of the patient and the trauma of the dental procedure. The use of fresh frozen plasma is effective in preventing attacks of angioedema in HAE patients undergoing all types of dental procedures.


Available online at: (small fee)

Funding for Canadian Hereditary Angioedema Network has been generously provided by unrestricted grants from:


CSL Behring


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