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Methenamine mandelate with acidification: an effective urinary antiseptic in patients with neurogenic bladder.

We studied the effectiveness of methenamine mandelate in preventing urinary tract infection in patients with neurogenic bladder dysfunction who were in a program of intermittent catheterization and bladder retraining. Nine of 17 patients (53%) became infected while receiving the drug, whereas 19 of 22 patients (86%) in a placebo group became infected during the trial. The difference in infection rates was statistically significant (P less than 0.02) and resulted primarily from the absence of gram-positive cocci and Pseudomonas species in the drug group.

Adolescent↗

Improved periodic acid-silver methenamine staining procedure for electron microscopy.

Mucosubstances can be stained for electron micrsocopy with silver methenamine after periodic acid oxidation in ultrathin Epon sections mounted on nickel grids. The grids are transferred from a solution to another during the staining procedure conveniently in a container made of polyvinyl chloride plastic. This staining procedure is easy to perform and gives reproducible results. It is especially suitable for simultaneous handling of a large number of grids.

Glycosaminoglycans↗

Localization of silver deposits on Pneumocystis carinii treated with Gomori's methenamine silver nitrate stain.

The question which portion of the pellicle of Pneumocystis carinii is actually stained by the Gomori's methenamine silver nitrate (GMS) method was solved with the aid of electron microscopy. Silver particles were specifically deposited on the electron-lucent middle layer of the precyst, cyst and ruptured cyst, whereas such deposition was not found on the pellicle of the trophozoite, probably due to the absence of the electron-lucent middle layer in the trophozoite. These deposits increased in proportion to the duration of staining and to the thickness of the lucent middle layer. Therefore, the lighter colored organisms as observed under the light microscope are considered to be the precysts because they have thinner GMS-positive middle layers than those of cysts. So-called parentheses-like structures or rings are one of the most characteristic light microscopic features of P. carinii cysts when stained with GMS. The present study indicates that these structures must be of cyst wall origin rather than of cytoplasm origin, because the thickened part of the cyst wall showed a dense deposition of silver particles, probably corresponding to the parentheses-like structure. On the other hand we also observed, in the endogeny form of trophozoite, a thin GMS-positive layer in the parent pellicle though this pellicle showed no differences from those of daughter and common trophozoites when observed by means of ultrathin section microscopy.

Animals↗

Comparison of Papanicolaou's stain with the Gomori methenamine silver (GMS) stain for the cytodiagnosis of Pneumocystis carinii in bronchoalveolar lavage (BAL) fluid.

The cytodiagnosis of Pneumocystis carinii (PC) in bronchoalveolar lavage (BAL) fluids has traditionally required a special stain such as Gomori's methenamine silver (GMS) stain. Recent reports indicate that identification of foamy alveolar casts (FACs) with Papanicolaou's (Pap) stain may provide a sensitive and less complicated way of making the diagnosis. To confirm these observations, results on a series of 318 BALs were reviewed. PC was identified on 65 (20%) specimens from 54 patients. Pap stains and GMS stains were positive on 56 (86%) of these BALs. Pap stains were positive on seven (11%) specimens that had negative GMS stains. PC was later confirmed on these specimens by other methods. Only two (3%) BALs had positive GMS stains and negative Pap stains. The results of this study confirm other reports that show that PC can be sensitively diagnosed with the Pap stain. The authors suggest that routine special stains for PC are unnecessary on BALs.

Bronchoalveolar Lavage Fluid↗

Methenamine-hippurate and bacteriuria in the geriatric patient with a catheter.

Oral treatment with methenamine-hippurate (MH) in patients with an indwelling catheter has been found to reduce the need of frequent catheter exchange and the number of symptomatic infections. Bacteriuria, however, persists during MH treatment. The hypothesis that the therapeutic effect is due to a reduction in the number of bacteria, or a change in the pattern of strains was tested in a crossover study (2 x 6 weeks). MH treatment, 1 g twice daily, was compared to control periods in 52 patients. The majority of quantitative and qualitative bacterial cultures at 2-week intervals yielded 2--4 strains. Of the bacterial isolates, 50% were found on 4--6 occasions out of 6 possible. MH treatment had no significant influence on the pattern of various strains. A 30% decrease in the mean total bacterial count during MH treatment did not reach statistical significance (p approximately 0.07). It is suggested that prevention of catheter complications during MH treatment may be due to a physiochemical action on salt formation rather than a direct antibacterial effect.

Aged↗

Visualization of human predentin and hypomineralized areas of dentin by silver methenamine staining.

The light microscopic structure of human teeth was studied following silver methenamine staining, with and without previous oxidation in periodic acid. Predentin, hypomineralized dentin and carious dentin stained intensely, whereas highly mineralized dentin and calcospherites at the predentin-dentin junction did not show any reactivity when observed in the light microscope, even following demineralization in strong acid or in EDTA. The reactive sites of the pulp were confined to nuclei, nucleoli and a few thin fibers. This distribution of reactive sites is different from the distribution which is seen following von Kossa's silver stain, and from the distribution seen following silver stain methods for reticular fibers.

Dental Caries↗

Comparison of methenamine silver nitrate and Giemsa stain for detection of Pneumocystis carinii in bronchoalveolar lavage specimens from HIV infected patients.

Seventy-seven bronchoalveolar lavages from human immunosuppressive virus infected patients with pulmonary symptoms were examined routinely for the presence of Pneumocystis carinii, using Giemsa stain to detect trophozoites and methenamine silver nitrate to detect cysts. Thirty-seven samples were found positive with both methods, but a further 10 were diagnosed with Giemsa indicating that the trophozoite stain is more sensitive. As Giemsa stain is simple, quick, cheap and familiar to most microbiological laboratories it should be used for screening of samples to be examined for Pneumocystis carinii. In cases where trophozoites are not detected by Giemsa a supplementary cyst stain may be performed in order to rule out the presumably few cases where cysts are present as the only evidence of Pneumocystis carinii infection.

Acquired Immunodeficiency Syndrome↗

Immunodetection of Pneumocystis carinii in bronchoalveolar lavage specimens compared with methenamine silver stain.

Immunodetection of Pneumocystis carinii, based on immunofluorescence and use of a monoclonal antibody specific for an antigen located within the cyst wall and detectable after trypsin digestion only, was compared with a methenamine silver stain in 553 bronchoalveolar lavage specimens from immunosuppressed patients. P. carinii was found by immunofluorescence in 72 (86%) and by silver stain in 68 (81%) of the total of 84 positive samples detected by either or both of these methods.

Bronchoalveolar Lavage Fluid↗

Methenamine hippurate ('Hiprex') in the treatment of chronic urinary tract infections: a trial in a geriatric hospital.

Fifty-two patients, all of whom were more than 66 years-old and who were hospitalized for periods in excess of two years were treated for chronic urinary tract infection. All patients received a course of antibiotic treatment for seven to ten days and were then put onto treatment with methenamine hippurate 1 g twice daily for six months. Of the original fifty-two patients, twelve did not complete the six month course. During the six month period with "Hiprex' there were far fewer re-infections than in the previous six months during which time they had received intermittent antibiotic therapy and other long-term treatment. There were no adverse reactions and bacterial resistance did not occur.

Aged↗

Urinary tract infection after vaginal surgery. Effect of prophylactic treatment with methenamine hippurate.

One hundred and nine consecutive patients undergoing surgery for uterovaginal prolapse followed by indwelling urinary catheter for 3 days were randomized for prophylactic treatment with methenamine hippurate (MH) or no MH prophylaxis. Significantly less bacteriuria occurred in the MH-treated patient group. In particular, the opportunistic hospital flora appeared to be suppressed by MH treatment. It is suggested that MH prophylaxis, 1 g three times daily, be used in gynecological surgery followed by short-term urinary catheterization.

Aged↗

Silver methenamine impregnation: a useful adjunct to renal electron microscopy.

The application of silver methenamine impregnation (SMI) to renal electronmicroscopy (EM) has been relatively neglected, but the technique has proved to be a useful aid in renal biopsy diagnosis. Tissues for SMI were fixed in glutaraldehyde/osmium and were embedded in either L.R. White resin or Epon. En-bloc staining of tissue with uranyl acetate was undertaken, but this procedure is considered optional. In our hands the technique has been valuable in the rapid assessment of renal ultrastructure in "routine" biopsies and especially in the diagnosis of complex or subtle changes in a variety of subtypes of glomerulonephritis, including the early membranous, familial-Alport type, mesangiocapillary and difficult to classify categories.

Glomerulonephritis↗

The effect of short-term high-dose treatment with methenamine hippurate of urinary infection in geriatric patients with indwelling catheters. II. Evaluation by means of a quantified urine sediment.

The urine sediment of 12 geriatric patients with indwelling catheters was quantified by the glutaraldehyde-cytocentrifuge method prior to, during and after a clinical trial of methenamine hippurate (MH), 2 g x 3 daily given for 34 days as the sole therapeutic agent for the urinary tract infection. The median leukocyte concentration in the urine of these patients was 100 cells/microliter (Q1 - Q3 50-350), i.e. tenfold higher than the upper normal limits reported in healthy probands. The median bacteriuria in the control period was 12 x 10(5) bacteria/ml urine, interquartile range 10-60 x 10(5) bacteria/ml and extreme individual values 300-500 x 10(5) bacteria/ml. Hematuria, defined as greater than or equal to 24 erythrocytes/microliter urine, was not prominent and could not be correlated with MH treatment, nor with catheter changes. The reported observations suggest that short-term high-dose treatment with MH as sole therapeutic agent reduced pyruria and bacteriuria in the group of patients studied.

Aged↗

Methenamine-silver staining: a simple and sensitive staining method for senile plaques and neurofibrillary tangles.

An improved methenamine-silver impregnation method is presented which exhibits sensitivity for amyloid substances comparable to that of anti-beta protein immunostaining. In optimally treated sections, this technique stained both beta-amyloid deposits and neurofibrillary tangles, which are known to have a beta-pleated structure. This simple procedure allows a large number of sections to be stained for routine examination.

Alzheimer Disease↗

Combination of trimethoprim and methenamine hippurate in the treatment of acute urinary tract infections.

A new antimicrobial drug combination of trimethoprim and methenamine hippurate (TMP + MH) at 2 different dosages (100 + 500 mg and 200 + 1000 mg b.i.d.) was compared by a random double-blind technique with plain TMP (200 mg b.i.d.) and TMP-sulfamethoxazole combination (160 mg + 800 mg b.i.d.). Each of the 4 test groups of 40-47 patients with acute UTI was treated for 2 weeks. The successful response in the test groups varied from 91 to 98% and no statistical difference could be found between the groups. The side-effects were least common in the group treated with the lower dose of TMP-MH combination.

Acute Disease↗

Trimethoprim and methenamine hippurate. A new theoretical combination for the treatment of urinary tract infections.

The antibacterial interaction of methenamine hippurate (MH) and trimethoprim (TMP) was tested in vitro in 3 different media: urine, brain-heart broth and Mueller-Hinton broth. MH and TMP were found to have a synergistic interaction in chequer-board titration against 11/11 bacteria in urine. Low concentrations of MH (1/2 MIC) had an additive or synergistic effect with TMP against 14/14 bacteria in brain-heart broth and 20/26 bacteria in Mueller-Hinton broth. In addition, the growth of bacteria in urine from healthy subjects treated with TMP (200 mg), MH (1000 mg) or a combination of TMP + MH (200 + 1000 mg) twice a day for 5 days was compared. A synergistic or additive effect of TMP and MH was found against 14/16 strains. Antagonistic interaction was not found in any of the tests. Preliminary pharmacokinetic studies with TMP and MH showed no marked interaction between the drugs. The hydrolysis of MH to formaldehyde was inversely related to urinary pH, and at pH 5 most of the formaldehyde released from MH in urine was generated within 3 h. The results suggest that the combination of TMP and MH may be more efficient than TMP alone in the treatment of urinary tract infections.

Adult↗

Methenamine and its salts as urinary tract antiseptics: variables affecting the antibacterial activity of formaldehyde, mandelic acid, and hippuric acid in vitro.

The activities of formaldehyde and of mandelic and hippuric acids, alone and in combination, have been tested against some 300 strains of bacteria typical of those causing urinary tract infections. In a chemically defined medium, which resembles urine in many respects, formaldehyde had a mean minimal inhibitory concentration of 13 mug per ml. Activity was several fold lower in media (nutrient agar and tryptic soy agar) that contained significant amounts of protein. The activity of formaldehyde is virtually unaffected by pH in the range of 5 to 8. Mandelic and hippuric acids (2 mg per ml) have limited antimicrobial activity at acid pH values only. The combination of formaldehyde with mandelic acid (2 mg per ml) was additive, most markedly at pH 5; the formaldehyde-hippuric acid combination, however, did not appear to be additive. Our findings suggest that, at pH values between 5 and 6, an antibacterial concentration of formaldehyde will be generated from methenamine within approximately 1 hr after being excreted into the urine.

Anti-Infective Agents, Urinary↗

A necropsy case of interstitial nephritis probably related to cefazolin and methenamine.

It is the purpose of this paper to alert the medical community on the potential nephrotoxicity of certain agents among certain patients, especially with some types of renal insufficiency. A young man, who was suffering from apparent renal disturbance, died of massive, post-operative bleeding accompanied by uremia. The uremia occurred within a very rapid clinical course and was related apparently to treatment with methenamine, a ruinary disinfectant, and cefazolin, a cephalosporin derivative. The patient was proved to have a fatal, servere interstitial nephritis based on gross and histological findings of the necropsied kidney, i.e., intense cell infiltration mainly in the interstitum of the cortex, absence of glomerular involvement, and marked softening and enlargement. The present case may suggest how to treat patients suffering from untoward renal ailments with various antibiotics.

Adult↗

Periodic acid thiosemicarbazide gelatin methenamine silver (PATSC-GMS) staining for transmission electron microscopy.

A new electron microscopic method is described in which superior staining of basement membranes, collagen fibers and glycogen particles in various tissues was achieved. This method uses a gelatin methenamine silver solution applied to the ultrathin sections on nickel grids after oxidation in a periodic acid. The staining results were excellent and tissue components were evenly stained with no background silver grains. This method proved to be consistent, reproducible and reliable.

Animals↗