Search PubMed⌕ Search

Biomedical subjects

D P Griffith

Publications and source records attributed to D P Griffith.

At least 91 records · Page 5Linked to original sources
PubMed1978

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 complete dissolution of stones in 9 patients. Long-term chemotherapy with antimicrobial agents that achieve sterile urine or acetohydroxamic acid in those patients with recalcitrant infection lessens the risk of recurrent calculogenesis.

Adult↗
PubMed1978

Pharmacokinetics of acetohydroxamic acid. Preliminary investigations.

The pharmacokinetics of acetohydroxamic acid (AHA), an agent being evaluated in the treatment of infection-induced urinary stones, have been examined in rats and man. After oral and intravenous administration of AHA to rats the biologic half-life and total body clearance seemed to be dose dependent. Comparison of the oral and intravenous data indicated that less than 100 per cent of an oral dose of AHA reaches the systemic circulation intact and that this percentage is dose related. Studies performed in human subjects indicated that AHA is rapidly absorbed from the gastrointestinal tract and has a biologic half-life of 5 to 10 hr in subjects with normal renal function. The half-life and percent of dose recovered in the urine seem to be dose related and dependent upon renal function.

Administration, Oral↗
PubMed1976

Further observations on the potentiation of the antibacterial effect of methenamine by acetohydroxamic acid.

The use of methenamine in the treatment of urinary tract infections due to Proteus species is limited by urine alkalinity. Acetohydroxamic acid, an inhibitor of urease, maintains acidity despite growth of Proteus in urine. Easily achievable concentrations of acetohydroxamic acid in vitro systems that simulated the dynamics of the urinary tract potentiated the antibacterial effect of methenamine against Proteus species. The combined use of a urease inhibitor and methenamine may be effective in the treatment of urinary infection caused by these organisms.

Ammonia↗
PubMed1976

Dissolution of struvite urinary stones. Experimental studies in vitro.

Previous studies from our laboratory have shown that struvite crystals form primarily as a result of urease-induced alkalinity and supersaturation. In vitro perfusion of struvite crystals with undersaturated urine caused crystal dissolution. The investigations reported herein demonstrate complete dissolution of human struvite urinary stones during 6 weeks of perfusion in vitro with undersaturated human urine. Human hydroxyapatite stones perfused similarly underwent only slight dissolution. A glycoprotein precipitated as the stones dissolved; the pathogenic significance of the glycoprotein is unknown.

Apatites↗
PubMed1976

The generation of formaldehyde from methenamine. Effect of urinary flow and residual volume.

The antimicrobial effect of methenamine in urine is dependent upon: (i) the rate of generation of formaldehyde; (ii) the concentration of formaldehyde achieved; and (iii) the duration of bacterial exposure to formaldehyde. Studies utilizing an in vitro model which simulates the dynamics of the urinary tract showed that bacteriostatic concentrations of formaldehyde (greater than or equal to 25 mug per ml) were obtained from attainable concentrations of methenamine at urine pH 5.7 to 5.85. Reduced urinary flow rates and large residual volumes increased formaldehyde concentrations and would appear to provide prolonged bacterial exposure to the formaldehyde.

Formaldehyde↗
PubMed1976

Urease. The primary cause of infection-induced urinary stones.

Previous reports have suggested that urease-producing bacteria play a prominent role in the formation of infection-induced urinary stones. We have carried out crystalization experiments in vitro which show that bacterial urease alkalinizes urine, thereby causing: (i) supersaturation with respect to struvite and calcium phosphate; and (ii) formation of struvite and apatite crystals. Growth of Proteus in urea-free urine or in urine which contained a urease inhibitor did not cause alkalinization, supersaturation, or crystallization of struvite and apatite. Growth of Klebsiella, Escherichia coli, or Pseudomonas was not associated with significant alkalinization, supersaturation, or crystallization. Struvite and apatite crystals dissolved in Proteus-infected urine in which undersaturation was maintained by urease inhibition. Similar results in all experiments were obtained using human urine and a synthetic urine which was devoid of matrix, pyrophosphate, or other undefined solutes. Urease-induced supersaturation appears to be the primary cause of infection-induced urinary stones.

Bacteria↗
PubMed1975

Acetohydroxamic acid. Potential use in urinary infection caused by urea-splitting bacteria.

Several lines of evidence suggest that bacterial urease is the primary cause of infection-induced urinary stones. The hydroxamate group of compounds are specific urease inhibitors. Of the cogeners studied, to dat, AHA (acetohydroxamic acid) appears to have the most pharmacologic potential. AHA is rapidly and completely absorbed from the gastrointestinal tract and is concentrated and excreted in the urine. In animals it appears to be relatively nontoxic. Although its toxicity in human beings has not been studied, its similarity to hydroxyurea suggests that reversible toxicity involving the gastrointestinal tract and the hematopoietic systems may result when high doses are administered. The only known metabolite of AHA is acetamide which is nontoxic and rapidly excreted in the urine. Pharmacologic use of AHA is expected to be practical and relatively safe. Use of AHA in patients with urinary infections caused by urea-splitting bacteria may reduce pathogenicity of the infecting organism and may lead to prevention and/or dissolution of stones commonly associated with such infections.

Acetamides↗
PubMed1975

Sensitivity studies in bacteriologic diagnosis of urinary tuberculosis.

The identification of Mycobacterium tuberculosis organisms is insensitive. This in vitro investigation compares the sensitivity of Ziehl-Neelsen and fluorochrome staining techniques after two and ten hours of incubation with standard culture techniques. The culture methods were persistently more sensitive than the stain techniques. Both stain techniques were of equal sensitivity. Ten hours incubation reduces the sensitivity of the staining techniques but does not alter the sensitivity of the culture methods.

Bacteriological Techniques↗
PubMed1975

Role of urease in pyelonephritis resulting from urinary tract infection with Proteus.

The role of urease in induction of pyelonephritis was studied by treatment of proteus-infected rats with acetohydroxamic acid, a potent inhibitor of urease. Infection was produced by introduction of Proteus mirabilis into the bladder along with a zinc disk. Controls were treated identically but received no acetohydroxamic acid. The number of bacteria per milliliter of urine was the same in both groups. The number of bacteria in the kidneys and the extent of renal damage was much greater in controls. Common enterobacteraceal antigen was not detected in the renal parenchyma of rats treated with acetohydroxamic acid. Treatment with acetohydroxamic acid thus prevented invasion of and damage to kidney tissue without reduction of urinary infection. Thus new evidence was found that the invasive properties of Proteus in the urinary tract are dependent on alkalinization of urine by urease and the resulting damage to the renal epithelium.

Acute Disease↗
PubMed1975

A comparative evaluation of Avitene and gelfoam for hemostasis in experimental canine prostatic wounds.

Microcrystalline collagen has been reported to be an effective hemostatic agent in brain, liver, kidney, etc. This experimental study in dogs and rats shows that microcrystalline collagen is a more effective hemostat in prostatic hemorrhage than is purified gelatin solution. No gross or histologic evidence of tissue damage or calcification was induced by microcrystalline collagen or purified gelatin solution. Wafers of microcrystalline collagen that are placed in rat bladders dissolve and do not induce calculogenesis.

Animals↗
PubMed1974

Potentiation of the antibacterial effect of methenamine by acetohydroxamic acid.

In vitro testing shows nearly all strains of Proteus to be susceptible to methenamine. However, infection by urease-producing bacteria alkalinizes the urine in vivo and prevents generation of formaldehyde, the active metabolite, from methenamine. We have previously shown acetohydroxamic acid (AHA) to be an effective inhibitor of bacterial urease in vitro and in vivo. We now present data obtained by use of static and dynamic in vitro systems, which show that, by preventing urease-induced alkalinization of urine, AHA enables methenamine to exert its antibacterial effect against representative Proteus species.

Drug Synergism↗
PubMed1974

Interaction between acetohydroxamic acid and 12 antibiotics against 14 gram-negative pathogenic bacteria.

Acetohydroxamic acid (AHA) is a potent inhibitor of urease which prevents alkalinization of urine and stone formation in rats in the presence of infection caused by urease-producing bacteria. Because an antibacterial effect of AHA, and synergy between kanamycin and AHA have also been described, we studied the interaction between AHA and 12 antibiotics against 14 gram-negative bacteria. Synergy, sometimes to a striking degree, was found in 17% of interactions; however, antagonism was detected in 5%. Infecting organisms would need to be studied individually before the antibacterial effect of AHA and an antibiotic could be predicted.

Anti-Bacterial Agents↗
PubMed1974

Generation of formaldehyde from methenamine: effect of pH and concentration, and antibacterial effect.

Using an in vitro system that simulates the dynamics of the urinary tract, we have shown that concentrations of formaldehyde >/= 25 mug/ml can be achieved in urine containing >/= 0.6 mg of methenamine per ml at pH </= 5.7 or >/= 1 mg/ml at pH </= 5.85. Exposure to this concentration of formaldehyde for 2 h produced a measurable antibacterial effect. These studies suggest that an effective bacteriostatic level of formaldehyde is likely to be achieved with currently used dosages of methenamine when the urine pH is less than 5.7 to 5.85.

Anti-Bacterial Agents↗