Acquired chronic candidiasis treated with transfer factor

A patient with acquired chronic oral and vaginal candidiasis resistant to topical and parenteral therapy was found to have impaired cell mediated immunity to Candida antigen and loss of skin test response to tuberculin (Mantoux). Treatment with Candida-active transfer factor produced clinical remission lasting 1 year and restitution of in vitro and in vivo immune parameters. Relapse occurred while receiving a second lot of transfer factor from the same donor. Subsequent treatment with levamisole was associated with onset of agranulocytosis.     

Celiac Disease with Jejunal Ulceration

A patient with celiac disease with ulceration of the jejunum, an infrequent association, is reported. Patient underwent surgery for resection of the ulcerated segment. The frequency of such an association, possible complications and an approach to therapy is reviewed.     

Dose Dependence of Covalent Binding of Acrylonitrile to Tissue Protein and Globin in Rats

The dose dependence of acrylonitrile (AN) covalent binding totissue protein, following a single acute exposure over a 100-foldrange in dose, was measured. Covalent binding was a linear functionof AN dose in the lower dose range (0.0–0.95 mmol AN/kg).The slopes of the dose-response curves indicated that tissuesvaried by nearly 10-fold in their reactivity with AN. The relativeorder of covalent binding was as follows: blood > kidney= liver > forestomach = brain > glandular stomach >muscle. Similar dose-response behavior was observed for globintotal covalent binding and for globin N-(2-cyanoethyl)vallne(CEValine) adduct formation. The latter adduct was found torepresent only 0.2% of the total AN adduction to globin. Regressionof tissue protein binding versus globin total covalent bindingor globin CEValine adduct indicated that both globin biomarkerscould be used as surrogates to estimate the amount of AN boundto tissue protein. At higher AN doses, above approximately 1mmol/kg, a sharp break in the covalent binding dose-responsecurve was observed. This knot value is explained by the nearlycomplete depletion of liver glutathione and the resultant terminationof AN detoxification. The toxicity of AN is known to increasesharply above this dose. The data suggest that a comparisonof specific tissue proteins labeled by AN above and below thisthreshold dose may provide some insight into the mechanism ofAN-induced toxicity.     

Biological Markers of Acute Acrylonitrile Intoxication in Rats as a Function of Dose and Time

Three markers of acute acrylonitrile (AN) intoxication, namely,tissue glutathione (GSH), tissue cyanide (CN), and covalentbinding to tissue protein, were studied as a function of doseand time. Doses administered and responses expected were 20mg/kg (LD0), 50 mg/kg (LD10), 80 mg/kg (LD50), and 115 mg/kg(LD90). Liver GSH was the most sensitive marker of AN exposure.At 80 mg/kg AN, virtually complete depletion of liver GSH wasobserved within 30 min with no recovery through 120 mm. KidneyGSH showed a similar, but less intense depletion; while bloodand brain GSH were more refractory to AN. Whole blood and brainCN rose progressively during the first 60 mm in a dose-dependentfashion. At the lowest dose, CN levels decreased thereafter,whereas, at the three higher doses, CN levels were maintainedor continued to increase through 120 min. At the highest dose,blood and brain CN remained at acutely toxic levels through240 mm. Covalent binding increased rapidly in all tissues duringthe first 30 mm at all doses. At the lowest dose, little additionalcovalent binding was observed beyond 30 mm, while at the threehigher doses, covalent binding increased, although at a slowerrate. The data indicate that these three biologic markers ofacute AN intoxication respond dramatically in a time-dependentmanner in the toxic dosage range. Furthermore, the data provideevidence that AN toxicity is gated by GSH depletion in liverwith the resultant termination of AN detoxification.     

Ventricular Arrhythmias in Dilated Cardiomyopathy

Although prognosis of dilated cardiomyopathy (DCM) has improved due to advances in diagnosis and therapy, still too many sudden cardiac deaths occur in DCM. Spontaneous ventricular ectopy is a very common finding in patients with DCM, but the prognostic significance of Holter monitoring remains controversial. Other noninvasive methods, e.g., late potentials and QT dispersion, have not yet contributed to the evaluation of prognosis for arrhythmogenic events in DCM. Programmed ventricular stimulation has been repeatedly used to stratify long-term prognosis, yet satisfactory data are still missing as many deaths occur in patients without inducible arrhythmias. Several prognostic studies are still in progess, and preliminary data for the use of ICDs already appear to be promising. In patients with poor left ventricular function and ICDs in situ, prognosis is determined by progression of heart failure. Heart transplantation may be the ultimate therapeutic instrument for end-stage heart failure patients. For patients with advanced DCM and increased risk for malignant arrhythmias who are unsuitable for orthotopic heart transplantation, the combined therapy with an ICD and dynamic cardiomyoplasty may be an alternative treatment.