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Biomedical subjects

C Merry

Publications and source records attributed to C Merry.

At least 19 recordsLinked to original sources
PubMed2004

Neurocysticercosis: a rare cause of seizure.

Neurocysticercosis is endemic in certain parts of the world, is rare in Europe and has never previously been described in the Irish healthcare setting. We report the case of a healthy male, originally from Guatemala, who presented to our hospital with a generalized tonic-clonic seizure presumed secondary to neurocysticercosis.

Adult↗
PubMed2000

Therapeutic drug monitoring of antiretrovirals in human immunodeficiency virus infection.

The era of antiviral therapy directed against HIV-1 has now entered its second decade. In the twelve years since the FDA approved the first antiretroviral drug zidovudine there have been a number of seminal developments that have revolutionized the approach to therapy. These advances converged to change the treatment paradigm from one of therapeutic nihilism to that of cautious optimism. First, several trials demonstrated that combination therapy of nucleoside reverse transcriptase inhibitors (NRTIs) is superior to monotherapy in extending survival and delaying disease progression. Second, the concept of virologic latency in asymptomatic HIV-infected patients was revised. Mathematic modelling demonstrated that there is an ongoing high level of virus production driving a rapid turnover of CD4 cells at all stages of infection. Hence it was concluded that the aim of antiretroviral therapy (ART) should be to "hit early and hit hard." Third, significant advances in molecular virology facilitated the development of quantitative methods to measure the circulating HIV plasma RNA. HIV viral load has been shown to be a sensitive predictor of disease progression and a valuable marker of response to therapy. However, none of these developments would have translated into improved patient care without the advent of two new classes of drugs-the protease inhibitors (PIs) and the nonnucleoside reverse transcriptase inhibitors (NNRTIs).

Anti-HIV Agents↗
PubMed1999

Interaction of sildenafil and indinavir when co-administered to HIV-positive patients.

OBJECTIVES: The prevalence of erectile dysfunction in HIV-infected men is estimated to be 33%. Sildenafil citrate (Viagra; Pfizer Ltd, Sandwich, Kent, UK) is the first oral drug for this condition. Since sildenafil and the protease inhibitors are both metabolized by, and act as inhibitors of cytochrome P450 3A4, we evaluated the pharmacokinetics of the combination sildenafil plus indinavir in HIV-infected patients. DESIGN AND METHODS: Six patients at steady state in treatment with indinavir participated in the study. On the first day blood samples for indinavir assay were drawn at times 0, 1, 2, 3, 4, 6 and 8 h after dosing. On the second study day patients received a single dose of 25 mg of sildenafil in addition to their routine morning medication. Blood samples were taken as described. Separated plasma was stored at -80 degrees C until analysis by high performance liquid chromatography. In a parallel study, the effect of indinavir, ritonavir, saquinavir and nelfinavir on the in vitro hepatic metabolism of sildenafil was assessed. RESULTS: The geometric mean area under the concentration curve for 0-8 h (AUC0-8h) and maximum plasma concentration (Cmax) for indinavir were 19.69 microg/ml h (range, 9.19-31.99 microg/ml h) and 7.02 microg/ml (range, 2.33-16.17 microg/ml), respectively, on the first study day. In the presence of sildenafil, the mean AUC0-8h and Cmax of indinavir were 22.37 microg/ml h [range, 10.08-37.25 microg/ml h; 95% confidence interval (CI) for difference between means, -15 to 13.25) and 9.11 microg/ml (range, 3.41-22.78 microg/ml; 95% CI, -13 to 6.37), respectively. The geometric mean AUC0-8h and Cmax for sildenafil were 1631 ng/ml h (range, 643-2970 ng/ml h) and 384 ng/ml (range, 209-766 ng/ml) respectively. The AUC for sildenafil was 4.4 times higher than data from historical controls given either 50 mg or 100 mg of sildenafil and dose normalized to 25 mg. Indinavir was a potent inhibitor of sildenafil hepatic metabolism in vitro [concentration producing 50% inhibition of control enzyme activity (IC50) = 0.39 +/- 0.17 microM, mean +/- SD]. CONCLUSIONS: Co-administration of sildenafil 25 mg did not significantly alter the plasma indinavir levels. However, plasma sildenafil AUC was markedly increased in the presence of indinavir compared with historical controls. From the in vitro data, the mechanism of increase is indinavir inhibition of the hepatic metabolism of sildenafil. The magnitude of this interaction suggests a lower starting dose of sildenafil may be more appropriate in this clinical setting.

Adult↗
PubMed1999

Resection of foregut-derived duplications by minimal-access surgery.

Eight children underwent minimal-access surgery (MAS) for duplications of foregut derivatives. The efficacy and safety of this approach are reviewed. The seven patients with mediastinal lesions had video-assisted thoracoscopic resection. One lesion presented as a subdiaphragmatic esophageal diverticulum, which was excised laparoscopically. Between March 1991 and October 1997, eight children were treated. Mean age was 27 months and mean weight was 11. 4 kg. Mean operating time was 106 min, and mean postoperative hospital stay was 4.5 days (median = 2 days). Persistent air leaks occurred in two patients who had centrally-located bronchogenic cysts. One of these, who had undergone subtotal excision with laser photoablation of the remaining cyst mucosa, developed a recurrence that was excised at thoracotomy. We conclude that esophageal and bronchogenic cysts and duplications may be safely excised by MAS in children, with excellent cosmetic and functional outcome. Two technical points are noted: (1) a thoracostomy tube is required for central mediastinal lesions; and (2) complete excision is required to prevent recurrence.

Bronchogenic Cyst↗
PubMed1999

Factors associated with prolonged symptoms and severe disease due to Clostridium difficile.

OBJECTIVE: toxigenic Clostridium difficile is responsible for a spectrum of disease severity ranging from mild diarrhoea to fulminant colitis. This study attempts to determine the proportion of patients in each category of severity and evaluate the risk factors for a more prolonged and complicated course. DESIGN: prospective cohort study. SETTING: university teaching hospital. SUBJECTS: all patients with symptomatic C. difficile infection during 4 months of an outbreak (January-April 1995); n=73; median age 74 years (range 17-91). MEASUREMENTS: incidence of C. difficile-associated disease (CDAD); severity of disease; percentage of patients in each category of severity; risk factors for severe disease/prolonged symptoms (univariate and multivariable analyses). RESULTS: the incidence of CDAD was 0.93%. Of the cases identified, 18 (24.7%) had mild, self-limiting disease; 26 (35.6%) had moderately severe disease; 23 (31.5%) had prolonged symptoms and six (8.2%) had a complicated course. Although CDAD was more common in older patients (P < 0.001), increasing age was not a risk factor for severity. Significant risk factors for severe CDAD included low Barthel and abbreviated mental test scores (P < 0.01, P < 0.001 respectively) and recent endoscopy (P=0.03). Logistic regression analysis revealed the following independent predictors of severe CDAD: endoscopy [odds ratios (OR) 4.0, P=0.03] and cognitive impairment (OR 11.0, P < 0.01). A trend towards significance was noted for nasogastric tube insertion (OR 3.1, P=0.08). Complications of infection included dehydration, malnutrition and faecal incontinence (which was statistically significantly associated with more severe disease; P < 0.01). CONCLUSION: risk factors for severity of CDAD include functional disability, cognitive impairment, and recent endoscopy. Anticipation of severe CDAD may limit morbidity and mortality.

Adolescent↗
PubMed1999

Pharmacokinetics and potential interactions amongst antiretroviral agents used to treat patients with HIV infection.

There are 3 groups of drugs available for the treatment of patients with HIV disease. These are the nucleoside reverse transcriptase inhibitors ('nucleoside analogues') [zidovudine, didanosine, zalcitabine, lamivudine and abacavir]; the non-nucleoside reverse transcriptase inhibitors (nevirapine, delavirdine and efavirenz); and the protease inhibitors (saquinavir, ritonavir, indinavir, nelfinavir and amprenavir). The preferred initial regimen should reduce and maintain plasma HIV RNA below the level of detection. Presently, the regimen of choice consists of 2 nucleoside analogues plus a protease inhibitor with high in vivo efficacy. An alternative combination consists of 2 nucleoside analogues plus a non-nucleoside reverse transcriptase inhibitor. Drug interactions are one of the major problems associated with these multidrug regimens. Changes in plasma concentrations of the nucleoside analogues are unlikely to be of clinical relevance as drug effect is mainly dependent on the rate and extent of intracellular phosphorylation. Combinations of zidovudine plus stavudine, and probably zalcitabine plus lamivudine, should be avoided as competition for phosphorylating enzymes may occur. The antiviral efficacy of some nucleoside analogues, e.g. stavudine, may be compromised by prior treatment with other nucleosides (e.g. zidovudine). However, these data need to be clarified in further studies. It is unlikely that administration of other antiretrovirals will influence the activity of nucleoside analogues. Protease inhibitors are metabolised by hepatic cytochrome P450 (CYP) 3A4. Combination protease inhibitor therapy can result in drug interactions mediated by enzyme inhibition. Ritonavir is the most potent inhibitor, saquinavir the least. The protease inhibitors also interact with the non-nucleoside reverse transcriptase inhibitors. Nevirapine and efavirenz induce drug metabolising enzymes and may reduce plasma concentrations of protease inhibitors. A study in healthy volunteers showed that nelfinavir concentrations are increased by combination with efavirenz. Delavirdine inhibits drug metabolising enzymes and increases the plasma concentration of coadministered protease inhibitors. The nucleoside analogues would not be expected to interact with the protease inhibitors. Apart from the ability of didanosine to reduce the area under the concentration-time curve of delavirdine, there are no reports of clinically significant interactions of other antiretrovirals with the non-nucleoside reverse transcriptase inhibitors. Triple therapy is the current standard of care for patients with HIV disease. However, studies of quadruple therapy are already under way. Drug interactions are likely to remain one of the major considerations when selecting a therapeutic regimen for patients with HIV.

Antiviral Agents↗
PubMed1998

The pharmacokinetics of combination therapy with nelfinavir plus nevirapine.

OBJECTIVE: To investigate the pharmacokinetics of nelfinavir (NFV) administered alone and in combination with nevirapine (NVP) to HIV-positive patients. DESIGN: Seven patients with advanced HIV disease received dual nucleoside analogues in addition to NFV (750 mg three times daily) and subsequently NVP (200 mg daily for 2 weeks followed by 200 mg twice daily) as salvage therapy. On the first study day (day 3), blood samples were taken for assay of NFV. The second study day followed the introduction of NVP for 3 weeks. METHODS: Blood samples were obtained at 0, 1, 2, 3, 4, 6 and 8 h after dosing on both study days. Separated plasma was heated to 58 degrees C for 30 min to inactivate HIV and stored at -80 degrees C until analysis by high performance liquid chromatography for both NFV and NVP. RESULTS: The geometric mean NFV area under the concentration-time curve to 8 h (AUC0-8h) was 23.4 microg x h/ml (range, 13.5-49.2) and 11.6 microg x h/ml (range, 6.6-23.2) on the first and second study days, respectively. The geometric mean ratio was 0.49 (95% confidence interval, 0.33-0.72; P = 0.016). This represented a 50% reduction in plasma NFV concentrations. Maximum and minimum concentrations were also reduced during NVP therapy (from 4.4 to 2.5 microg/ml and from 1.7 to 0.8 microg/ml, respectively). Time to maximum concentration was reduced from 4 to 2 h. NVP concentrations were determined with a maximum concentration of 5.4 microg/ml at 4 h. CONCLUSIONS: NVP is currently being used in combination therapy with protease inhibitors for antiretroviral-experienced patients in the setting of treatment failure. This study demonstrates that when patients are coadministered NVP there is a 50% reduction in the plasma AUC of NFV. Although the mean trough concentrations of NFV remained above the stated minimum effective concentration of 0.4 microg/ml, there is nevertheless concern that some patients will fall below this value when NVP is added to treatment regimens. In the absence of therapeutic drug monitoring we suggest that an increase in the standard NFV dosage of 750 mg three times daily will be required to ensure satisfactory NFV plasma concentrations, thereby maintaining antiviral efficacy.

Adult↗
PubMed1998

Laparoscopic pyloromyotomy: a safer technique.

A modified technique of laparoscopic pyloromyotomy was used to treat infantile hypertrophic pyloric stenosis. Introducing a 5-mm periumbilical port for visualization, two stab wounds are made on either side laterally to directly insert 2.7-mm instruments for manipulation. From the left, the stomach is grasped - not the duodenum! From the right, an inexpensive disposable arthroscopy knife is used to incise the serosa and begin the myotomy, which is completed with a laparoscopic spreader until the muscle is separated sufficiently to relieve the obstruction. Twenty-nine children treated with laparoscopic pyloromyotomy were compared to 125 children treated with the conventional open Ramstedt pyloromyotomy. There were no statistically significant differences in the presentation or results between groups, suggesting that the laparoscopic technique is a safe and equal alternative.

Female↗
PubMed1998

Community-acquired Clostridium difficile infection.

Clostridium difficile-associated disease (CDAD) is primarily a nosocomial condition. Community-acquired disease has been reported but the incidence is felt to be low and the rate of disease resulting in hospitalization is reported as negligible. We recently experienced a 6-month outbreak of CDAD (January to June 1995): 139 patients were involved and four deaths were attributable to pseudomembranous colitis. Early in the outbreak period we were aware that many new admissions presented with C. difficile cytotoxin B positive diarrhoea: in some cases this was the sole reason for hospitalization. This observation forms the basis of this report.

Adult↗
PubMed1998

Simultaneous outbreaks of two strains of toxigenic Clostridium difficile in a general hospital.

We report an outbreak of Clostridium difficile-associated disease (CDAD) in a large Dublin hospital. From January to June 1995, inclusive, 139 patients were affected; the mean age of cases was 68.8 +/- 19 years. Clinical information is available for 73 cases identified during the first four months of the outbreak. The majority of patients presented with abrupt onset of watery diarrhoea; however, 19.2% presented with an unexplained pyrexia following a course of antimicrobial therapy and 5.5% presented with a surgical acute abdomen. Twenty patients (27.4%) experienced relapsing disease and seven (9.6%) patients died. Seventy-six percent of cases received a cephalosporin prior to the onset of disease, the highest relative risks occurring with third-generation agents; however, 9.6% of patients affected had not been exposed to antimicrobial therapy in the preceding eight weeks. Pyrolysis mass spectrometry identified two clusters of isolates, representing two strains of C. difficile. There was marked spatial clustering of these strains, with each confined to a separate area of the hospital. Infection control measures and an antibiotic policy were introduced. Throughout the outbreak period the use of the most frequently used cephalosporin in the hospital increased; this was accompanied paradoxically by a reduction in the number of new cases of CDAD.

Aged↗