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Biomedical subjects

M J Wolin

Publications and source records attributed to M J Wolin.

At least 19 recordsLinked to original sources

Digoxin visual toxicity with therapeutic blood levels of digoxin.

PURPOSE: To report two cases of digoxin-related visual disturbances associated with therapeutic blood levels of digoxin. METHODS: Case reports. One patient reported shimmering lights in the field of vision of both eyes; the second patient had a corrected visual acuity of BE, 20/40 and generalized visual field depression in both eyes. Both patients experienced these symptoms while receiving digoxin. RESULTS: Both patients had digoxin blood levels in the therapeutic range (1.7 and 1.0 ng/ml, respectively). Therapeutic levels are 0.5 to 2.0 ng/ml. After discontinuing digoxin, the first patient noted that the shimmering light symptoms resolved, and the second patient had improved visual acuity and visual fields. CONCLUSIONS: Digoxin-related visual toxicity may be associated with therapeutic blood levels of digoxin. Recognition of this entity may avoid unnecessary testing and frustration.

Aged

Changes in production of ethanol, acids and H2 from glucose by the fecal flora of a 16- to 158-d-old breast-fed infant.

Microbes in the adult human colon ferment dietary substrates chiefly to acetic, propionic and butyric acids and CO2, H2 and CH4. How this fermentation evolves after microbial colonization of the neonate is unknown. We examined the fermentation of glucose by fecal suspensions of a breast-fed infant from d 16 to 158 and found that the fermentation changed with age. Acetate, ethanol, succinate, lactate, formate and H2 were formed up to 117 d of age. Production of succinate, lactate, formate and H2 ceased after 117 d and acetate production increased. Butyrate and propionate were minor products up to 117 d. Afterwards, there was a slight increase in propionate production with no change in butyrate formation. Acetate was always the major product of glucose fermentation by the fecal suspensions. Approximately the same amounts of ethanol were formed throughout the study period. The fermentations were similar to fermentations of Escherichia coli and streptococci through 117 d. Nuclear magnetic resonance (NMR) analysis of the acetate formed from 1-13C- and 3-13C-glucose showed that the dominant fermentation pathway used by the colonic microbes switched from the Embden-Meyerhof-Parnas pathway at 16 d of age to the Bifidobacterium pathway at 158 d of age. An increase in the contribution of the Bifidobacterium fermentation to the overall colonic fermentation after 117 d would account for the increase in the formation of acetate from glucose. Chemical and NMR analyses of products of fecal fermentations from two other breast-fed infants <1 mo old were similar to those of the infant examined between 16 and 158 d.

Acetates

NMR detection of 13CH313COOH from 3-13C-glucose: a signature for Bifidobacterium fermentation in the intestinal tract.

The gastrointestinal tracts of breast-fed infants are colonized more easily with bifidobacteria than are those of formula-fed infants. Colonization is thought to reduce infant diarrhea. Amendments to formulas that improve colonization by bifidobacteria are being actively investigated. Colonization studies almost invariably require measurements of the concentration of the bifidobacteria in feces to assess their importance in the colon. We investigated the use of nuclear magnetic resonance (NMR) analysis of products of fermentations of 1- and 3-13C-glucose to evaluate the importance of bifidobacteria in the colonic ecosystem. Bifidobacteria use a unique pathway of hexose catabolism to produce primarily acetate and lactate. The fermentation yields 3 mol of acetate from 2 mol of glucose. Two of the acetates are formed from C1 and C2 of glucose and the third is formed entirely from C3 of glucose. We first employed high resolution NMR to verify the pathway used by a pure culture of Bifidobacterium bifidum. The major products of fermentation of 1- and 3-13C-glucose were acetate and lactate. Most of the 13C from 3-13C-glucose was in 13CH313COOH with equal enrichment in the methyl and carboxyl groups. The 13C-acetate from 1-13C-glucose was almost entirely enriched in the methyl of acetate and no 13CH313COOH was produced. NMR analysis of glucose fermentation by the colonic flora of a 158-d-old strictly breast-fed infant showed production of 13CH313COOH from 3-13C-glucose. The amount of 13CH313COOH formed established that the Bifidobacterium pathway was the major pathway used for glucose fermentation by this infant's colonic microbes.

Acetic Acid

Therapy of acute myelogenous leukemia: understanding the question, understanding the answer.

The best therapy for people with acute myelogenous leukemia (AML) in first remission is controversial. Options include postremission chemotherapy, a bone marrow transplant (HLA-identical sibling or autotransplant) or chemotherapy followed by a transplant at relapse. Four large cooperative group trials address this issue. In this review design and implementation of these trials is considered. Whether data from these trials will answer the questions of the best therapy for AML in first remission, is focused upon.

Antineoplastic Agents

Acarbose enhances human colonic butyrate production.

Earlier studies suggest that butyrate has colonic differentiating and nutritional effects and that acarbose increases butyrate production. To determine the effects of acarbose on colonic fermentation, subjects were given 50-200 mg acarbose or placebo (cornstarch), three times per day, with meals in a double-blind crossover study. Fecal concentrations of starch and starch-fermenting bacteria were measured and fecal fermentation products determined after incubation of fecal suspensions with and without added substrate for 6 and 24 h. Substrate additions were cornstarch, cornstarch plus acarbose and potato starch. Dietary starch consumption was similar during acarbose and placebo treatment periods, but fecal starch concentrations were found to be significantly greater with acarbose treatment. Ratios of starch-fermenting to total anaerobic bacteria were also significantly greater with acarbose treatment. Butyrate in feces, measured either as concentration or as percentage of total short-chain fatty acids, was significantly greater with acarbose treatment than with placebo treatment. Butyrate ranged from 22.3 to 27.5 mol/100 mol for the 50-200 mg, three times per day doses of acarbose compared with 18.3-19.3 mol/100 mol for the comparable placebo periods. The propionate in fecal total short-chain fatty acids was significantly less with acarbose treatment (10.7-12.1 mol/100 mol) than with placebo treatment (13.7-14.2 mol/100 mol). Butyrate production was significantly greater in fermentations in samples collected during acarbose treatment, whereas production of acetate and propionate was significantly less. Fermentation decreased when acarbose was added directly to cornstarch fermentations. Acarbose effectively augmented colonic butyrate production by several mechanisms; it reduced starch absorption, expanded concentrations of starch-fermenting and butyrate-producing bacteria and inhibited starch use by acetate- and propionate-producing bacteria.

Acarbose

In vitro activities of ciprofloxacin and rifampin alone and in combination against growing and nongrowing strains of methicillin-susceptible and methicillin-resistant Staphylococcus aureus.

We characterized the effects of ciprofloxacin and rifampin alone and in combination on Staphylococcus aureus in vitro. The effects of drug combinations (e.g., indifferent, antagonistic, or additive interactions) on growth inhibition were compared by disk approximation studies and by determining the fractional inhibitory concentrations. Bactericidal effects in log-phase bacteria and in nongrowing isolates were characterized by time-kill methods. The effect of drug combinations was dependent upon whether or not cells were growing and whether killing or growth inhibition was the endpoint used to measure drug interaction. Despite bactericidal antagonism in time-kill experiments, our in vitro studies suggest several possible explanations for the observed benefits in patients treated with a combination of ciprofloxacin and rifampin for deep-seated staphylococcal infections. Notably, when growth inhibition rather than killing was used to characterize drug interaction, indifference rather than antagonism was observed. An additive bactericidal effect was observed in nongrowing bacteria suspended in phosphate-buffered saline. While rifampin antagonized the bactericidal effects of ciprofloxacin, ciprofloxacin did not antagonize the bactericidal effects of rifampin. Each antimicrobial prevented the emergence of subpopulations that were resistant to the other.

Anti-Infective Agents

Neuro-ophthalmologic manifestations of adenoid cystic carcinoma.

Intracranial adenoid cystic carcinoma is uncommon. We report two unusual cases of intracranial adenoid cystic carcinoma. The first patient presented with a steroid-responsive optic neuropathy from an orbital mass that simulated orbital pseudotumor, and subsequently developed intracranial involvement, presumably by contiguous perineural spread. The second patient presented with proptosis of the left eye, right facial weakness and numbness, and an intracranial mass, presumably from hematogenous metastatic spread.

Adult

Oculopalatal myoclonus after the one-and-a-half syndrome with facial nerve palsy.

PURPOSE: The one-and-a-half syndrome is an eye movement disorder characterized by a unilateral gaze palsy and an ipsilateral internuclear ophthalmoplegia. The authors describe a previously unrecognized association between the one-and-a-half syndrome and oculopalatal myoclonus (OPM). METHODS: Five clinical cases are presented, with pertinent physical findings and radiologic studies. RESULTS: A previously unrecognized association of the one-and-a-half syndrome with subsequent development of OPM appears to exist. Involvement of the facial nerve in patients with the one-and-a-half syndrome may be a predictor of the subsequent development of OPM. CONCLUSION: Patients with the one-and-a-half syndrome and facial nerve palsy should be followed closely for possible future development of OPM.

Adult

Pathways of acetate, propionate, and butyrate formation by the human fecal microbial flora.

The pathways of short-chain fatty acid (SCFA; acetate, propionate, and butyrate) formation from glucose were determined for the human fecal microbial communities of two subjects. The pathways were identified by radioisotope analysis of the SCFA and CO2 obtained after incubation of fecal suspensions with glucose under 20% CO2 with [1-14C]glucose, [3,4-14C]glucose, or 14CO2. Acetate was chemically degraded to learn the labeling of the methyl and carboxyl carbons. The labeling of CO2 and acetate showed that the major route of glucose catabolism was the Embden-Meyerhof-Parnas pathway, with production of CO2 from pyruvate carboxyl carbon. Labeling of the methyl and carboxyl carbons of acetate by 14CO2 or [3,4-14C]glucose proved that acetate was formed from CO2 by the Wood-Ljungdahl pathway. CO2 reduction accounted for about one-third of the acetate formed by suspensions from subject 1 and about one-fourth of the acetate formed by suspensions from subject 2. Propionate was formed by a CO2 fixation pathway, and butyrate was formed by classical routes of acetyl-S coenzyme A condensation. The amount of CO2 formed from [1-14C] glucose and acetate labeling patterns obtained with the other 14C precursors indicated that the Entner-Doudoroff, transketolase-transaldolase, and heterolactic pathways were not significant. Fermentation of cabbage cellulose by subject 1 followed the same pathways as were used for glucose. The results with suspensions from subject 2 suggested that some radioactive acetate was formed from the C-3 of glucose by the Bifidobacterium pathway.

Acetates

Acute graft-versus-host disease in a recipient of a twin blood cell transplant.

There are reports of acute graft-versus-host disease (GVHD) after autologous and twin bone marrow transplants but they are controversial because of the difficulty of accurate diagnosis. We report a subject with Philadelphia chromosome-positive CML who received two syngeneic transplants of blood cells. In the first transplant of 2.6 x 10(8) mononuclear cells/kg, no pretransplant conditioning was given; in the second transplant of 4.9 x 10(8) mononuclear cells/kg, pretransplant conditioning therapy consisted of chemotherapy and TBI. Although no symptoms were seen after the first transplant, the second was followed by fever, diarrhea, rash and liver function test abnormalities coincident with engraftment. Symptoms resolved spontaneously. The patient was not on any medication and had not received any transfusions. Our observations suggest either that acute GVHD in a twin transplant is a direct consequence of conditioning or that pretransplant conditioning is a prerequisite for developing features resembling acute GVHD.

Acute Disease

Digitalis-induced visual disturbances with therapeutic serum digitalis concentrations.

OBJECTIVE: To assess the role of digitalis in the development of visual symptoms severe enough to warrant ophthalmologic consultation in patients who received digitalis and who had no other clinical or laboratory evidence of digitalis toxicity. DESIGN: Clinical case study. SETTING: Neuro-ophthalmology referral practice. PATIENTS: Six elderly patients (aged 66 to 85 years) who received digitalis were referred to ophthalmologists for evaluation of photopsia (five patients) or decreased visual acuity (one patient). No patient had chromatopsia or nonvisual clinical manifestations of digitalis intoxication at the time of examination. MEASUREMENTS: All patients had serum digitalis concentrations within or below the therapeutic range. In most patients, the electroretinographic cone b-wave implicit time was longer than normal. RESULTS: Discontinuation of digitalis therapy, which was possible in five patients, was followed by resolution of visual symptoms and by shortening of the b-wave implicit time. Characteristic features of digitalis-induced photopsia were its dependence on illumination and its tendency to be localized in peripheral visual fields. CONCLUSIONS: In an elderly patient receiving digitalis, the development of photopsia characterized by innumerable points of light in the peripheral visual fields or a decrease in visual acuity raises the possibility that the patient's visual disturbance may have been digitalis induced. Digitalis-induced visual disturbances other than chromatopsia or disturbances of color vision may occur in elderly patients who have no other clinical manifestations of digitalis intoxication and who have a serum digitalis concentration within or below the therapeutic range.

Aged

Serum stem cell factor levels in patients with aplastic anemia.

Immune suppression of hematopoiesis has been implicated in the pathogenesis of acquired aplastic anemia. Similarly, abnormalities of T cells and bone marrow stromal cells have been reported in aplastic anemia, as has abnormal cytokine production. Stem cell factor (SCF) (also known as kit ligand, mast cell growth factor and Steel factor) is an early acting hematopoietic growth factor that is produced by a variety of mesenchymal cells including bone marrow stromal cells. To determine whether abnormalities in the production of stem cell factor occur in aplastic anemia, we evaluated serum levels of SCF in 25 patients with aplastic anemia. The mean serum levels of SCF in aplastic anemia patients were significantly lower (2.7 +/- 1.1 ng/ml) than those found in a comparable population of 257 normal controls (3.3 +/- 1.1 ng/ml) (P = 0.011). The SCF level did not correlate with patient age, the duration of aplastic anemia or with white blood cell count, platelet count or hematocrit. Although there is no direct evidence that lower SCF serum levels contribute to the pancytopenia seen in this disorder, identification of underlying abnormalities that can result in the deficient production of stromally derived hematopoietic growth factors will be important.

Adolescent

Alzheimer's disease and the eye.

AD patients may have substantial defects in the visual system despite a normal routine eye exam. Specific methods should be utilized to assess the ability of these patients to understand what they see and read. Subtle defects of eye movements may be present. Problems with contrast sensitivity, color vision, and stereo vision may be also be present, as well as early signs of optic atrophy. An awareness of the specific problems that AD patients present will lead the clinician to accurate diagnosis.

Alzheimer Disease

Bacterial strains from human feces that reduce CO2 to acetic acid.

We used dilutions of fecal suspensions from a human volunteer to enrich cultures for bacteria that reduce CO2 to acetate in the colon. The soluble enrichment substrates used were glucose, methanol, formate, and vanillate, which were used with a gas phase that contained 80% N2 and 20% CO2. The gaseous enrichment substrates used were 80% H2-20% CO2 and 50% CO-50% CO2. We isolated three different strains that produced acetate from CO2. One strain produced acetate from methanol, vanillate, H2-CO2, glucose, and other sugars. The other two strains did not form acetate from methanol or vanillate. Both of the latter strains formed acetate from glucose and other sugars, but only one of these strains formed acetate from H2-CO2. Both of these strains cometabolized formate. However, none of the enrichment cultures or pure cultures used CO or formate as a substrate for growth. The two strains that produced acetate from H2 and CO2 grew slowly when the gases alone were used as substrates, but they rapidly cometabolized H2 and CO2 when they were grown with organic substrates. The ability of all of the strains to produce acetate from CO2 and/or other one-carbon precursors was verified by determining the radioactivity of the methyl and carboxyl groups of the acetate formed after growth with 14CO2 or other radioactively labeled one-carbon precursors.

Acetates

Amounts of viable anaerobes, methanogens, and bacterial fermentation products in feces of rats fed high-fiber or fiber-free diets.

We investigated the impact of dietary fiber on the fecal output of microorganisms and microbial fermentation products of rats. Two groups of five male Wistar rats were fed high-fiber (HF) and fiber-free (FF) diets in the following order: (group 1) lab chow-->HF-->FF-->HF and (group 2) lab chow-->FF-->HF-->FF. Daily fecal output of total viable anaerobes was 71 times higher with the HF diet. Daily output of methanogens was 1.4 times higher for the HF diet than for the FF diet. Daily excretion of total fermentation acid products (acetate, propionate, butyrate, lactate, succinate, and formate) was 2.4 and 0.1 mmol for HF and FF diets, respectively. The ratios of acetate/propionate/butyrate were 69:21:10 for the HF diet and 92:7:1 for the FF diet. The results show that an HF diet significantly increases microbial growth in the colon and influences the proportions of organic acid products. The HF diet did not increase the ratio of methanogens to total anaerobes. We suggest that the contribution of host-derived substrates to colonic microbial growth and fermentation is insignificant.

Animals

Calcified brain metastasis.

Two patients with rare cases of calcified brain metastases are reported. The relatively benign clinical course and prolonged survival are stressed. The first patient had an adenocarcinoma of unknown origin with three calcified brain metastases. The patient underwent an incisional brain biopsy without radiotherapy and survived for 2 years and 9 months. The second patient had a squamous cell carcinoma of the lung with a large, solitary brain metastasis. The brain tumor was calcified and remained stable without progression for at least 4 months before surgical resection.

Adenocarcinoma