Nonlactating-cow therapy with a formulation of penicillin and novobiocin: therapeutic and prophylactic effects

An experimental product incorporating 500,000 IU of procaine penicillin G and 600 mg of sodium novobiocin in 2% aluminum monostearate-peanut oil gel (10-ml dose) was infused after the final milk-out at end of lactation into all 4 mammary quarters of 56 cows that were infected in at least 1 quarter. The therapeutic and prophylactic efficacies were published in the companion report. Infusion of the product in all quarters of 5 lactating cows resulted in only slight irritation. Penicillin was eliminated by the 11th milking and novobiocin by the 5th. After infusion in the dry udder, the antibiotics were no longer detectable in serous secretion after 14 days and failed to appear in urine at the earliest (7-day) sampling after administration. Neither antibiotic was detectable in the 1st postpartum milking after nonlactating periods as short as 3 weeks.     

Correlation of cerebral blood flow with outcome in head injured patients

In order to determine the relationship of cerebral blood flow (CBF) to the clinical outcome of head injury, serial determinations of CBF were performed by the intravenous Xenon technique in 24 patients. The patients were of mixed injury severity and were classified into four groups depending on the neurological exam at the time of each CBF study. All eight patients who were lethargic on admission demonstrated increases in their minimally depressed CBF as they improved to normal status. Eleven patients in deep stupor or coma ultimately recovered. Ten of these patients initially had moderate to profound decreases in CBF which improved as recovery occurred. The single exception was an adolescent whose initial CBF was high but became normal at recovery. Five comatose patients died. In four of these, already depressed CBF fell even lower, while one adolescent with initially increased CBF developed very low CBF preterminally. The data presented in this report demonstrated a good correlation between CBF and clinical outcome. In every one of the adult survivors, depressed CBF increased as the patient recovered to normal status. All adults who died showed a deterioration of CBF as the neurological status worsened. The only exceptions were two adolescents who initially showed high CBF values. In the adolescent who died, CBF dropped to low levels while in the survivor a normal CBF was achieved. Thus in adults a traumatic brain injury was associated with depressed CBF which increased with recovery or decreased further with deterioration while the reaction to injury was quite different in the younger brain.     

Theoretical analysis of the binding of salicylate by human serum albumin: the relationship between free and bound drug and therapeutic levels

The binding of salicylates by human serum albumin was analyzed by use of a computer program using previously published association constants and binding capacities for the two sets of binding sites on the protein. The analysis consisted of computing free and bound salicylates for a range of therapeutic and toxic concentration from 181 to 7246 mumole/L (25 to 1000 mg/L). At low and therapeutic levels the total amount of bound drug would exceed the amount of free drug. At higher levels, which included therapeutic and toxic ranges, the amount of free drug plasma, up to 2000 mumole/L the high affinity sites (Site 1), would bind most of the drug, but as the concentration of drug increased this site would approach saturation and the low affinity Site 2 would bind increasing amounts of salicylate. At high salicylate levels the amount of drug bound by the low affinity sites. Computation also showed that when the total amount of protein in the analysis was reduced, from 5, 4, 3, to 2 gm%, as in hypoalbuminemia, the total amount of drug bound by the protein would decrease and the quantity of free drug would increase. The amount of drug bound by each of the two sets of sites also fell as the concentration of protein decreased. Some of the possible clinical implications of these findings are discussed.     

Effects of low-intensity ultrasound on the central nervous system of primates

The brains of anesthesized squirrel monkeys were exposed to 2.25 to 5 MHz ultrasound at low intensities (average power from 3 mW/cm2 to 0.9 W/cm2). The exposure produced evoked potentials recorded by EEG electrodes chronically implanted in the midline parietal region. Computer analysis of the waveforms showed that ultrasound produced a transient upward shift in both the peak frequency and in its amplitude. Complete adaptation occurred with 3 min of continuous exposure to either CW or pulsed irradiation.     

Cyanogen bromide treatment of methionine-containing compounds

The preparation of a series of X-Met-Gly-OEt and X-Met-Phe-OMe and their treatment with CNBr in either 70% or 97-100% formic acid at 25 degrees C are described where X is methanesulfonyl (mesyl), p-nitrobenzyloxycarbonyl, phthaloyl, trifluoroacetyl, acetyl, formyl, or tert-butyloxycarbonyl. Total cleavage of the peptide esters was found with mesyl-, p-nitrobenzyloxycarbonyl-, phthaloyl-, and trifluoroacetylmethionyl derivatives which indicated the suitability of these derivatives as amino protecting groups in peptide synthesis. Treatment of the acetylmethionyl peptide esters with CNBr in 70 and 97-100% formic acid resulted in 92 and 98% cleavage, respectively. With formylmethionyl peptide esters, about 85-95% cleavage was estimated when either 70 or 97-100% formic acid was used as the solvent. With the tert-butyloxycarbonylmethionyl derivatives, CNBr treatment in 70% formic acid resulted in about 93% cleavage of peptides, while treatment in 97-100% formic acid led to only 30-33% release of C-terminal amino acid esters. Quantitative cleavage of the carbonylbis(methionyl peptide esters) was observed. The reaction of CNBr with N-terminal methionyl derivatives containing free alpha-amino groups revealed that free methionine was quantitatively converted to homoserine lactone, whereas methionine ethyl ester and methionyl peptides (Met-Gly and Met-Phe) disappeared from the reaction mixture in 70% formic acid with only partial splitting of the ester (16%) or peptide bond (45%).     

Acetohexamide hypoglycemia: treatment by peritoneal dialysis

Acetohexamide hypoglycemia in a patient with renal failure has been successfully treated by peritoneal dialysis. Peritoneal dialysis was done in such a patient, and specimens of serum were collected to measure levels of acetohexamide and its main active metabolite, hydroxyhexamide. During dialysis, hypoglycemia was corrected. After 17 1/2 hours of dialysis, serum acetohexamide level was essentially unchanged. Serum hydroxyhexamide level had decreased at a slower rate than the rate of decrease previously measured in a uremic patient not on dialysis. Although peritoneal dialysis may correct the hypoglycemia, the data suggest that acetohexamide and hydroxyhexamide are not dialyzable. Due to these problems this drug should not be used in patients with chronic renal failure. The drug of choice to control hyperglycemia in patients with renal insufficiency is insulin. If for any reason insulin cannot be used, tolbutamide is the oral hypoglycemic agent of choice.