Are the drug-regulatory agencies paper villains?
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Biomedical subjects
Publications and source records attributed to T Smith.
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The mechanism of isomerization of delta 5-3-ox steroids to delta 4-3-oxo steroids was examined by using the membrane-bound 3-oxo steroid delta 4-delta 5-isomerase (EC 5.3.3.1) and the 3 beta-hydroxy steroid dehydrogenase present in the microsomal fraction obtained from full-term human placenta. (1) Methods for the preparation of androst-5-ene-3 beta, 17 beta-diol specifically labelled at the 4 alpha-, 4 beta- or 6-positions are described. (2) Incubations with androst-5-ene-3 beta, 17 beta-diol stereospecifically 3H-labelled either in the 4 alpha- or 4 beta-position showed that the isomerization reaction occurs via a stereospecific elimination of the 4 beta hydrogen atom. In addition, the complete retention of 3H in the delta 4-3-oxo steroids obtained from [4 alpha-3H]androst-5-ene-3 beta, 17 beta-diol indicates that the non-enzymic contribution to these experiments was negligible. (3) To study the stereochemistry of the insertion of the incoming proton at C-6, the [6-3H]androst-4-ene-3, 17-dione obtained from the oxidation isomerization of [6-3H]androst-5-ene-3 beta, 17 beta-diol was enzymically hydroxylated in the 6 beta-position by the fungus Rhizopls stolonifer. Retention of 3H in the 6 alpha-position of the isolated 6 beta-hydroxyandrost-4-ene-3, 17-dione indicates that in the isomerase-catalysed migration of the C(5) = C(6) double bond, the incoming proton from the acidic group on the enzyme must enter C-6 from the beta-face, forcing the existing 3H into the 6 alpha-position.
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A study of hemolytic streptococci from clinical infections in dogs revealed the presence of four serogroups, with one to four biotypes in each, based on carbohydrate fermentation patterns. Of 254 isolates tested, 206 belonged to Lancefield group G, 30 to group C, 7 to group E, and 1 to group A. Ten isolates could not be grouped. Reactions on the three key carbohydrates, lactose, trehalose, and sorbitol, revealed four biotypes each in groups G and C, and two in group E and among the ungroupable cultures. The most common pattern, seen in 154 cultures, was lactose fermentation with no action on trehalose and sorbitol, and corresponded to that described for Streptococcus canis (Stafseth et al., J. Am. Vet. Med. Assoc. 90:769-781, 1937). Most of the strains originated from skin, subcutaneous and wound infections, genitourinary lesions, otitis externa, and respiratory disease. Data suggest that group G streptococci may be preferentially parasites of the urogenital tract.
Effects of pressure on cerebrospinal fluid (CSF) formation were studied in dogs with a recirculatory spinal perfusion tracer clearance technique that does not require steady-state conditions. The data permit statistical analysis of the relationship between the rate of CSF formation and pressure for individual animals. Most animals showed no statistical relationship between CSF formation and intracranial pressure (ICP) and/or cerebral perfusion pressure (CPP). In this study, a disturbance of cerebral blood flow (CBF) autoregulation may have been present in five animals on the basis of CPP reductions, and four of this latter group showed formation to decrease with increasing ICP. It is suggested that CSF formation is normally pressure insensitive. With impaired autoregulation of CBF, formation may follow CBF and CPP passively.
With the possible exception of ECF, body electrolyte spaces and pools can be measured with fair accuracy and are useful in their proper experimental context. The use of improved tracer techniques and mathematical analysis to study transfer rates between pools and the physiological factors which influence these rates offer a promising means of further progress in this field.
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Eaton-Lambert syndrome is most frequently associated with small-cell carcinoma of the lung. We describe the first case of this disorder in a patient with malignant thymoma. Guanidine treatment had no clinical or electrophysiologic effects.
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The records of 109 patients with non-Hodgkin's lymphoma of nodular pattern were reviewed to determine which factors were associated with a favorable response to therapy and prolonged survival. A logistic regression model was utilized to identify the pertinent variables. Prognostic factors associated with a favorable response were, in order of decreasing importance: treatment with an Adriamycin combination regimen, absence of bulky tumor, and no exposure to prior chemotherapy. Thos associated with prolonged survival were: normal hemoglobin level, treatment with an Adriamycin combination regimen, female sex, and no prior exposure to therapy. Achievement of complete remission in these disorders resulted in a statistically longer duration of survival compared to partial responses or failures. Patients whose complete remission was induced with an Adriamycin-containing regimen and maintained with BCG immunotherapy had a significantly longer complete remission than those who did not receive BCG. Knowledge of these factors can be important in planning and analyzing future therapeutic trials.
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