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M T Fallon

Publications and source records attributed to M T Fallon.

At least 19 recordsLinked to original sources
PubMed2000

The cognitive and psychomotor effects of morphine in healthy subjects: a randomized controlled trial of repeated (four) oral doses of dextropropoxyphene, morphine, lorazepam and placebo.

Ten healthy subjects (four male) of mean age 31 years (range 25-40) took part in a randomized double-blind four-way crossover study to examine the cognitive and psychomotor effects of repeated oral doses of dextropropoxyphene and morphine. Four treatments were compared: dextropropoxyphene napsylate 100 mg, morphine sulphate 10 mg, lorazepam 0.5 mg and placebo. Four doses of each drug were given at 4-h intervals to each subject on four separate study days at least 1 week apart. Cognitive function was assessed using choice reaction time, number vigilance, memory scanning, immediate and delayed word recall, word recognition, picture recognition, critical flicker fusion threshold (CFFT) and subjective measures of alertness, calmness and contentment. Lorazepam impaired the speed of responding on all tasks in which speed was recorded (except digit vigilance) and increased subjective ratings of calmness. Morphine had one major effect, which was to increase the accuracy of responding on the choice reaction time task, at every assessment. Morphine produced some sporadic effects in other tests and an increase in subjective calmness. Dextropropoxyphene impaired performance on choice reaction time and picture recognition. These data show that oral morphine may enhance performance in some measures of cognitive function, whereas dextropropoxyphene (in usual therapeutic doses) seems more likely to cause impairment. Neither opioid has substantial effects on cognition and psychomotor function compared with lorazepam.

Adult↗
PubMed1999

Use of cefazolin microspheres to treat localized methicillin-resistant Staphylococcus aureus infections in rats.

BACKGROUND: In a previous study, the topical administration of biodegradable, controlled-release poly-(dl-lactide-co-glycolide) cefazolin microspheres could effectively prevent surgical wound infections with a sensitive strain of Staphylococcus aureus in an experimental animal model. The objective of the current study was to evaluate and compare the efficacy of topical antibiotic therapy with cefazolin microspheres to systemic cefazolin therapy for the treatment of experimental rat surgical wounds contaminated with a methicillin-resistant strain of S. aureus (MRSA). METHODS: A local infection model in rats was used. MRSA was used to infect pockets surgically produced in the paraspinous muscles. Groups of rats received either topical cefazolin microspheres, topical cefazolin powder, parenteral cefazolin, or no treatment. Feces were cultured to evaluate the effect of antibiotic therapy on gut flora. RESULTS: The rate of clinical wound infection following topical application of cefazolin microspheres (13%) was significantly lower than the 53% infection rate observed in rats who had received a 2-week course of systemic cefazolin therapy (P = 0.046). Moreover, single-dose topical antibiotic therapy with cefazolin microspheres completely eradicated MRSA from the wounds of 7 of 15 (47%) animals. There was no statistically significant difference, however, in the rate of clinical wound infection between rats whose wounds were treated topically with free cefazolin powder and those treated with systemic cefazolin (P = 0.12). Importantly, selection of antibiotic-resistant bacteria was associated with systemic but not local cefazolin therapy. CONCLUSION: The results of this study suggest that topical antibiotic therapy with controlled-release cefazolin microspheres may be effective for the prevention of wound infection with both methicillin-sensitive and methicillin-resistant strains of S. aureus in selected surgical procedures that are at high risk of developing postoperative wound infection.

Administration, Topical↗
PubMed1998

Symptomatic hypocalcemia with oral clodronate.

We present a patient with prostate cancer who developed symptomatic hypocalcemia while taking oral clodronate for painful bony metastases. He had a past history of a bowel resection for Crohn's disease, and, although he was normocalcemic prior to taking clodronate, it is likely that the surgery had caused mild hyperparathyroidism. The addition of clodronate prevented the chronic osteolysis of bony metastases, which would have helped maintain normocalcemia. The case was complicated by hypomagnesemia and hypokalemia resulting from diarrhea. Hypomagnesemia is a cause of refractory hypocalcemia and hypokalemia. This case illustrates two important points. First, care must be taken with bisphosphonates in patients with a previous bowel resection. Second, magnesium plays a key role in the metabolism of both calcium and potassium, and must be considered in the evaluation of the hypocalcemic patient.

Administration, Oral↗
PubMed1997

Neurofilament heavy chain-like messenger RNA and protein are present in benign prostate and down-regulated in prostatic carcinoma.

Differences in gene expression between benign and malignant human prostate specimens were investigated using the differential display technique. RNA samples from paired benign and malignant areas microdissected from opposite sides of the same prostate gland were used for reverse transcription PCR. A 477-bp band was identified that was consistently present in benign prostate but absent or diminished in intensity in malignant tissue. This band was cloned, and the sequence demonstrated 99% identity with a region in the fourth exon of the human neurofilament heavy chain gene (NF-H). Northern blotting with a cDNA probe derived from this band confirmed the presence of a similarly sized message of approximately 3.9 kb in both prostate and brain, and reverse transcription PCR using primers specific to an upstream region of exon 4 confirmed NF-H-like mRNA expression in benign prostatic tissue. Immunostaining with a monoclonal antibody to NF-H showed a positive reaction in benign prostatic epithelial cells but complete absence of staining in prostatic cancer cells. These data demonstrate the presence of a NF-H-like gene product in normal prostatic epithelial cells that is down-regulated or absent in prostatic carcinomas.

Base Sequence↗
PubMed1997

Delayed local treatment of rabbit tibial fractures with biodegradable cefazolin microspheres.

The prevention of infection is a primary objective in the treatment of open fractures. The objective of this study was to compare the efficacy of biodegradable, poly (DL-lactide-co-glycolide) cefazolin microspheres and free cefazolin powder in Staphylococcus aureus contaminated rabbit tibial fractures when treatment was delayed for 2 hours. Fractures were produced in the tibia of rabbits, inoculated with Staphylococcus aureus, and 2 hours later treated by either direct local application of cefazolin microspheres or an equivalent dose of free cefazolin powder. Control animals did not receive antibiotic therapy. The fractures then were stabilized with a bone plate, and the animals were observed for 8 weeks. Local antibiotic therapy with biodegradable cefazolin microspheres prevented the establishment of infection in all animals, and cultures of the tibiae were sterile in all cases. In contrast, clinical evidence of infection developed in 50% of the rabbits that had been treated with free cefazolin powder and 71% of the control animals. Staphylococcus aureus was recovered from the tibiae of 75% and 100% of these animals, respectively. The results of this study suggest that local antibiotic therapy with biodegradable, controlled release cefazolin microspheres may be useful for the management of open fractures in humans, even when treatment is delayed for several hours after bacterial contamination.

Animals↗
PubMed1996

Intravenous vs. intraprostatic administration of N-methyl-N-nitrosourea to induce prostate cancer in rats.

To develop an improved model of human prostate cancer, 16-wk-old Wistar rats were treated orally for 18 days with the antiandrogen, flutamide (50 mg/kg body weight [BW]/day), followed by 3 days of s.c. testosterone (100 mg/kg BW). There were the only treatments the control animals received (Group 1, n = 10). On the day after the third testosterone injection, N-methyl-N-nitorsourea (MNU) was administered via the tail vein at a dose of 50 mg/kg BW (Groups 2, n = 40 and 3, n = 20); in some rats, a second dose was delivered by the same route 22 wk later (Group 3). A smaller dose of MNU (15 mg/kg BW) was administered intraprostatically (Group 4, n = 20) to a fourth group. In Groups 2, 3, and 4, silastic capsules containing testosterone were implanted s.c. approximately every 6 wk beginning 1 wk post-MNU. Accessory sex gland tumors arose in MNU-treated rats in Group 2 (12/40, 30%). Group 3 (8/20, 40%), and Group 4 (8/20, 40%); 90% were macroscopic (25/28). There were no neoplasms in these organs in the control rats (Group 1, 0/10). These accessory sex gland neoplasms were adenocarcinomas or undifferentiated carcinomas which appeared to be derived from the prostate based on location and histological characteristics, although the size and spread of some of the tumors precluded definitive localization of the tissue of origin. The incidence of these neoplasms was similar in rats given a single dose of MNU intraprostatically or two doses of MNU i.v., but the animals treated intraprostatically maintained higher body weights and developed fewer extraneous tumors. The average (+/- SD) latent period for clinical or postmortem detection of prostate neoplasia after MNU was shortest in the rats given two i.v. doses (39 +/- 3 wk) compared with the single i.v. dose (45 +/- 6 wk) or an intraprostatic dose (56 +/- 7 wk). In 57% of the cases (16/28), the prostate tumors metastasized to distant sites. An activating point mutation was detected in codon 12 of the Ki-ras oncogene in the MNU-induced primary prostate tumors (8/10 examined), and metastases arising from these prostate tumors (2/3) but was absent in normal prostate tissue (0/6). This study demonstrates that two systemic doses of MNU increase the incidence and decrease the latency of prostate neoplasms compared with a single dose, and that a single dose of MNU injected intraprostatically induces prostate adenocarcinoma without many of the other tumors and weight loss typically found after i.v. administration.

Adenocarcinoma↗
PubMed1995

Evaluation of maduramicin and alborixin in a SCID mouse model of chronic cryptosporidiosis.

Two polyether ionophores, maduramicin and alborixin, were evaluated for anticryptosporidial activity in a severe combined immune deficient (SCID) mouse model of cryptosporidiosis. Groups of SCID mice were inoculated with 10(6) oocysts of bovine origin by oral gavage. Maduramicin or alborixin was administered beginning 4 weeks postinfection at 3 mg/kg of body weight per day. Maduramicin treatment resulted in a 96% reduction in fecal parasite load over the 3-week treatment period (P < 0.003). This reduction correlated with decreases in tissue parasite loads observed in histological sections of the small intestine (P < 0.000002) and the colon (P < 0.000006). A significant decrease in oocyst shedding was also observed after a 3-week treatment with alborixin (71% reduction, P < 0.01). Maduramicin was also evaluated in a relapsing model of cryptosporidiosis in which the infection was observed to recur after treatments were discontinued. Some toxicity, as demonstrated by weight loss, was observed with both maduramicin and alborixin. Both drugs exhibited significant anticryptosporidial activities with concomitant moderate toxicity. These polyether ionophores should be valuable as positive controls in compound evaluation studies and as lead compounds for chemical optimization (modification).

Animals↗
PubMed1994

Infection dynamics and clinical features of cryptosporidiosis in SCID mice.

Cryptosporidial infections in severe combined immune deficient (SCID) mice produce a chronic disease state which in the later stages leads to extraintestinal involvement and hepatic dysfunction. To further characterize the infection dynamics in this model and monitor the changes in the hepatic system, a dose titration of the oocyst inoculum was performed and alkaline phosphatase levels in the sera were assayed. Ten SCID mice per dose were inoculated with 10(3), 10(4), 10(5), 10(6), or 10(7) oocysts. Oocyst shedding in the feces was quantified by microscopic enumeration. Mice inoculated with 10(6) oocysts and those inoculated with 10(7) oocysts demonstrated similar oocyst shedding patterns, but the 10(7)-oocyst group exhibited signs of distress (e.g., weight loss and icterus) earlier. The intensity of the infection increased markedly approximately 14 days postinoculation (p.i.) and continued to increase steadily over the next 6 weeks. Inoculation with lower oocyst doses produced a delay in patency (e.g., it occurred 7 days later with the 10(5)-oocyst inoculum and 14 days later with the 10(4)-oocyst inoculum). Mean serum alkaline phosphatase levels in the 10(7)-oocyst group were more than twice control values at 5 weeks p.i. and continued to increase over the next 8 weeks. Oocyst doses and alkaline phosphatase levels were positively correlated with hepatobiliary colonization (r = 0.71) and liver necrosis (r = 0.65) at 13 weeks p.i. A strong positive correlation between hepatobiliary colonization and liver necrosis at 13 weeks p.i. (r = 0.87) was observed.

Alkaline Phosphatase↗
PubMed1994

Control of common symptoms in advanced cancer.

In common with any medical problem, careful assessment and an analytical approach are the keystones to effective symptom control in advanced cancer. When dealing with such symptoms the multi-faceted pathophysiology must be considered, and due attention paid to the affective component of pain and other symptoms. Adequate care given to history taking and a knowledge of the likely pathogenesis of symptoms in advanced cancer can prevent unnecessary investigations and fruitless trials of inappropriate symptomatic remedies. The treatment chosen should be the simplest effective regimen tailored to the individual patient. The importance of explanation to the patient cannot be overstated and is an integral part of any treatment and the sole component of many. This paper reviews the management of common symptoms in advanced cancer (dyspnoea, nausea and vomiting, constipation, anorexia-cachexia syndrome, hypercalcaemia, confusion, insomnia and depression.

Anorexia↗
PubMed1993

Paradoxical pain.

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Drug Resistance↗
PubMed1993

Evaluation of biodegradable cefazolin sodium microspheres for the prevention of infection in rabbits with experimental open tibial fractures stabilized with internal fixation.

Immediate internal fixation of severe open tibial fractures usually is contraindicated due to the high risk of infection. The objective of this study was to evaluate the efficacy of local antibiotic therapy with biodegradable poly-(DL-lactide-co-glycolide) cefazolin-loaded microspheres for the prevention of infection in experimental open fractures stabilized with internal fixation. Rabbits with experimental tibial fractures that were contaminated with Staphylococcus aureus were treated with local application of cefazolin microspheres, an equivalent local dose of free Ancef powder, or systemic Ancef therapy. The bones then were fixed with a four-hole plate, and the animals were observed for 8 weeks. Clinically, deep infection was present in 86% of control animals that received no antibiotics and in 60% of animals that received a 7 day course of systemic Ancef therapy. In contrast, no infections were noted among any of the surviving rabbits that received local therapy with either cefazolin microspheres or free Ancef powder. Significantly higher levels of serum cefazolin were measured at 1 h for animals treated with free Ancef powder (18.7 +/- 6.1 micrograms/ml) than for those treated with cefazolin microspheres (0.57 +/- 0.27 micrograms/ml). Follow-up studies are in progress to evaluate further the potential clinical benefits of local antibiotic therapy for the management of contaminated open fractures in humans.

Animals↗
PubMed1991

Mouse hepatitis virus strain UAB infection enhances resistance to Salmonella typhimurium in mice by inducing suppression of bacterial growth.

We have previously shown that intranasal infection of mice with mouse hepatitis virus (MHV) strain UAB (MHV-UAB) increases their resistance to Salmonella typhimurium injected intravenously 6 days later. To study how salmonella resistance was induced, BALB/cAnNCr mice were infected with salmonella strains carrying specific genetic alterations. One set of studies compared the effect of MHV infection on subsequent salmonella infections with AroA- (avirulent) and Aro+ (virulent) salmonellae. Unlike its effect on Aro+ salmonellae, MHV failed to reduce the number of AroA- salmonellae recovered from mice. Because AroA- S. typhimurium shows almost no growth in vivo, this failure indicated that the effect of MHV on salmonella resistance required growth of the infecting salmonellae. In other studies, the effect of MHV infection on both growth and killing were monitored simultaneously in mice with growing salmonellae carrying a single copy of the temperature-sensitive pHSG422 plasmid, which is unable to replicate in vivo. MHV infection reduced salmonella growth but caused no increase in salmonella killing. MHV infection of mice given wild-type salmonellae also resulted in no increase in salmonella killing 4 h after salmonella challenge. These studies demonstrate that MHV-UAB infection increases host resistance to salmonellae by enhancing suppression of bacterial growth instead of by increasing the amount of salmonella killing.

Animals↗
PubMed1989

Modulation of resistance to Salmonella typhimurium infection in mice by mouse hepatitis virus (MHV).

Prior infection of mice with a field strain of mouse hepatitis virus (MHV) increased the early resistance of euthymic mice to virulent Salmonella typhimurium strain SR-11 infections (as defined by significantly fewer salmonella colony-forming units (cfu) present in spleens and livers 4 days after salmonella infection). This increase in salmonella resistance was observed when the interval between MHV and salmonella infections was 6 days, but not at 3, 10, or 14 day intervals. The mouse Ity locus, which controls the number of intracellular salmonella, had a significant effect on the ability of MHV to induce resistance to salmonella. MHV caused an increase in resistance to salmonella in Itys (salmonella susceptible) mice at all doses of salmonella tested (100 to 10,000 cfu). In the Ityr (salmonella resistant) mice tested the beneficial effect of MHV on salmonella resistance was small and when observed, was only present at salmonella doses of 10,000 cfu or greater. Neither the Lpsd nor Xid mutations affected the ability of MHV to increase resistance to salmonella infection. In contrast to euthymic mice, MHV infection greatly decreased the resistance of athymic (nude) mice to salmonella infection. Since the Nu locus does not affect the resistance of mice to salmonella (at 4 days post salmonella infection), these results indicate that MHV infection and the nude phenotype interact to increase susceptibility to salmonella. These findings re-emphasize the importance of keeping laboratory mice used in research free of MHV and other immunomodulatory pathogens.

Adjuvants, Immunologic↗