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D P Griffith

Publications and source records attributed to D P Griffith.

At least 73 records · Page 4Linked to original sources
PubMed1985

Pharmacokinetics of acetohydroxamic acid in patients with staghorn renal calculi.

Acetohydroxamic acid (AHA), a bacterial urease inhibitor, has been recently approved by the United States Food and Drug Administration as a potential drug for the successful treatment of patients with infection induced staghorn renal calculi. The present study was designed to evaluate the disposition of 14C-AHA following oral administration to patients. The results of the study, while in a limited number of patients, indicate that upon oral administration, AHA is very rapidly absorbed from the gastrointestinal tract. Evaluation of urinary excretion data suggests that patients with compromised renal function have low recoveries of AHA in the urine. These data are supported by a strong linear correlation between creatinine clearance and AHA elimination. Acetamide and CO2 are identified as the two major metabolites of AHA in man. CO2 is eliminated in the breath and accounts for 20-45% of the administered dose, while acetamide is eliminated in the urine and accounts for only 9-14% of the administered dose. The remaining dose is eliminated as intact AHA in the urine (19-48%). Saliva concentrations of total radioactivity depict a strong positive correlation with their respective plasma concentrations. Parameter estimates from 14CO2 concentrations in breath as a function of time data closely correspond to the pharmacokinetic parameters of AHA in patients indicating that CO2 may be a primary metabolite derived directly from AHA rather than a secondary metabolite formed by the metabolism of an intermediate product. Upon multiple dose administration of AHA, there is the potential for significant accumulation of acetamide due to its relatively long half-life.

Acetamides↗
PubMed1984

Effect of ammonium on bacterial adherence to bladder transitional epithelium.

The virulence of urease-producing bacteria depends on the ability of urease to degrade urea into ammonia and thereby to alkalinize the urine. Infections caused by urease-producing organisms such as Proteus mirabilis are particularly difficult to manage clinically. We have shown that the layer of glycosaminoglycans at the bladder surface protects against infection by blocking the adherence of bacteria to the epithelium. To determine whether urease-producing urinary pathogens owe their virulence in part to an ability to inactivate the protective effect of the glycosaminoglycan layer, we tested the ability of ammonium chloride to alter bacterial adherence to the normal vesical mucosa. We used an in vivo adherence assay that we have described previously in rabbits. Control animals received sodium chloride adjusted to the same pH as the ammonium chloride. We found that 0.25 M ammonium chloride significantly increases bacterial adherence to normal vesical mucosa as compared to adherence in controls receiving 0.25 M sodium chloride (p less than 0.05). These data suggest that urease plays a hitherto undescribed role in bacterial virulence by altering the antiadherence activity of the glycosaminoglycan layer present at the transitional cell surface.

Adhesiveness↗
PubMed1984

Evaluation of a calculolytic diet in female dogs with induced struvite urolithiasis.

The calculolytic effect of a diet designed to reduce the urine concentration of urea, P, and Mg was evaluated in female Beagles with induced urease-positive urinary tract infections and struvite urolithiasis and in female Beagles with induced sterile struvite urolithiasis. The reduced-protein calculolytic diet induced urolith dissolution in 5 of 6 infected dogs with struvite urolithiasis in 2 to 5 months (means = 14.4 weeks). At the end of 6 months, uroliths in comparable control dogs fed a maintenance diet were 5 times larger and 14 times heavier than at the beginning of the study. The calculolytic diet induced urolith dissolution in 6 of 6 noninfected dogs with struvite uroliths in 2 to 4 weeks (means = 3.3 weeks). Four uroliths in noninfected dogs fed the maintenance diet dissolved over a period of 2 to 5 months (means = 14 weeks). Urolith dissolution in dogs fed the calculolytic diet was associated with diet-induced diuresis, reduction in urine pH, reduction in urine concentration of urea ammonia, P, and Mg, and increase in urine titratable acidity. Consumption of the calculolytic diet was also associated with significant (P = less than 0.01) reduction in the serum concentration of urea and albumin and a significant (P = less than 0.01) increase in serum hepatic alkaline phosphatase activity. Concomitant occurrence of hydropic degeneration of hepatocytes indicated that these biochemical and morphologic changes were associated with dietary protein restriction.

Animals↗
PubMed1981

Canine struvite urolithiasis: problems and their dissolution.

Struvite (magnesium ammonium phosphate) uroliths are found more frequently in the urinary tracts, of dogs than are other types of uroliths. Infection of the urinary tract with urease-producing bacteria, especially staphylococci, plays an important role in urolith formation. An inherited predisposition to urinary tract infection may be associated with the high rat of occurrence of struvite uroliths in some dogs. Diagnosis of struvite urolithiasis should encompass analysis of the mineral composition of calculi and identification of concomitant urinary tract infection. Since urinary tract infections occur as sequelae to abnormalities in local or systemic host-defense mechanisms, appropriate effort should be directed toward detection of these abnormalities. Therapy of struvite urolithiasis should encompass relief of obstruction to outflow when necessary, elimination of existing calculi, eradication or control of urinary tract infection, and prevention of recurrence. Although surgical removal remains as the preferred method to eliminate struvite uroliths from dogs, nonsurgical methods of urolith dissolution should be considered. Recurrence of struvite uroliths may be prevented by various combinations of antimicrobial therapy, administration of urease inhibitors, acidification of urine, and induction of diuresis.

Animals↗
PubMed1981

Mineral composition of urinary calculi from miniature schnauzer dogs.

The mineral composition of 150 calculi from the urinary tracts of Miniature Schnauzer dogs was determined by qualitative and quantitative methods. Struvite was the predominant mineral in 92% of the calculi. Other calculi contained predominantly apatite, calcium oxalate, ammonium urate, or silica. Most calculi were from the urinary bladder or urethra, or both. Four were from the renal pelves. Struvite calculi were more frequently encountered in females than males. The mean age of the dogs at the time of detection of calculi was 4.8 years. Qualitative analysis failed to detect some minerals that were identified by quantitative analysis.

Animals↗
PubMed1981

Urolithiasis.

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Europe↗
PubMed1980

Struvite urolithiasis in a litter of miniature Schnauzer dogs.

Magnesium ammonium phosphate calculi developed in the urinary bladders and urethras of four of five offspring of Miniature Schnauzer parents with recurrent struvite urolithiasis. Calculi were detected by radiograhy when the dogs were 12 to 15 months old. Males and females were affected. A significant number of urease-producing staphylococci were identified in the urine of three of four dogs before urolith formation, and in one dog after urolith formation. The dogs were evaluated until they were 26 months old. Serum concentrations of calcium, phosphorus, and magnesium were inside usual limits throughout the study. Abnormalities that might predispose to urinary tract infection were not identified by radiography or necropsy studies. In one dog, bladder calculi recurred after surgical removal of multiple cystoliths. In another, urethral obstruction and acute generalized pyelonephritis induced a lethal uremic crisis. Gross and microscopic lesions, detected after necropsy of all dogs with uroliths, were typical of bacterial infection.

Animals↗
PubMed1980

Experimental induction of struvite uroliths in miniature schnauzer and beagle dogs.

Urease positive staphylococcal urinary tract infection was experimentally induced in 13 dogs. Eight dogs developed cystic and/or urethral struvite calculi in 2 to 8 weeks. No abnormalities in systemic cell mediated immunity were detected in dogs before or after the establishment of the urinary tract infection. Miniature schnauzers whose ancestors had developed stones seemed to be no more susceptible to experimental urinary tract infection and stone formation than miniature schnauzers or beagles whose ancestors did not develop stones.

Animals↗
PubMed1979

Urease stones.

Urinary stones form as a consequence of urinary supersaturation. Supersaturation occurs as a result of elevated concentrations of urinary solutes. Dietary, metabolic, endocrine, hereditary, and infectious processes alter urinary solute concentrations. Struvite (MgNH4PO. 6H2O) and carbonate-apatite [Ca10(PO4)6CO3] stones form in urine that becomes supersaturated as a by-product of the hydrolysis of urea by the bacterial enzyme urease. Urease-induced stones manifest primarily as branched renal calculi and as bladder calculi. Conventional therapy has usually consisted of surgical removal of the stone combined with a short course of antimicrobial therapy. Such treatment is curative in about 50% of cases. Recurrent stone formation and progressive pyelonephritis occur in those who are not cured. Adjunctive medical treatment with acetohydroxamic acid or hydroxyurea lessens the risk of calculogenesis and decreases growth of residual stones in patients who are not cured by conventional therapy. Patients with urea-splitting urinary infection and renal stones have a major life-threatening disease. The morbidity and expense that result from this disease are great. Long-term (perhaps lifetime) chemotherapy with antimicrobial agents and/or urease-inhibiting drugs combined with judicious and expert surgical intervention can be expected to significantly improve the plight of these unfortunate patients.

Adult↗
PubMed1979

Adjunctive chemotherapy of infection-induced staghorn calculi.

Bacteria induce urinary crystallization of struvite and carbonate-apatite as a by-product of ureolysis by urease. Eradication of infection and/or inhibition of urease with acetohydroxamic acid for 5 to 30 months retarded stone growth and brought about partial or comple dissolution of stones in 9 patients. Long-term chemotherapy with antimicrobial agents that achieve steril urine or acetohydroxamic acid in those patients with recalcitrant infection lessens the risk of recurrent calculogenesis.

Adult↗
PubMed1978

Acetohydroxamic acid: clinical studies of a urease inhibitor in patients with staghorn renal calculi.

The hydrolysis of urea by the bacterial enzyme urease pathologically increase urinary ammonia, bicarbonate, carconate and alkalinity. These factors contribute to the formation of urinary stones and to the virulence of bacteria. Acetohydroxamic acid, a potent inhibitor of urease, has been administered to 23 patients with staghorn renal calculi and urea-splitting urinary infection. Urinary ammonia and alkalinity has been reduced in every patient. A dose of 1.0 gm. acetohydroxamic acid daily has been well tolerated and effective for 2 to 12 months, even in patients with impaired renal function.

Ammonia↗
PubMed1978

Struvite stones.

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Adult↗