The development of resistance to anthelmintics: a perspective with an emphasis on the antischistosomal drug praziquantel.
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Animals↗
Biomedical subjects
M Ismail
Publications and source records attributed to M Ismail.
Color Doppler imaging in predicting the biologic behavior of prostate cancer: correlation with disease-free survival.
OBJECTIVES: We investigated the association of transrectal color Doppler imaging (CDI) signal detection in localized prostate cancer with biologic behavior as assessed by tumor Gleason grade, seminal vesicle invasion, capsular and margin status, and actuarial biochemical freedom from relapse. METHODS: From 1991 to 1996, transrectal ultrasound with CDI and biopsy was performed in 2718 men using a 7.0-MHz probe optimized to detect color-coded blood flow within the gland and along the capsular margin. Color flow was graded on a scale from 0 to 2+, with 0 and 1+ representing no detectable flow and normal flow, and 2+ indicating increased flow. Color flow maps were constructed in 47 men with clinically localized prostate cancer treated by radical prostatectomy (RP) and compared to their whole mount RP specimen step sections. RESULTS: Color flow detected within the index tumor was graded as 2+ in 22 of 47 patients and 0 or 1+ in the remaining 25. Tumors graded 2+ correlated with higher Gleason grade, higher incidence of seminal vesicle invasion, and higher relapse rate, with only 11 of 22 patients disease free based on undetectable prostate-specific antigen (PSA) levels. In contrast, 24 of 25 patients with tumors graded 0 or 1+ are free of biochemical relapse with a median follow-up of 30.9 months. Patients with increased flow were 10.2 times more likely to relapse even after correction for other prognostic variables. In addition, tumors with 2+ capsular flow correlated with a higher incidence of non-organ-confined disease. CONCLUSIONS: Color-coded Doppler flow within the tumor and overlying capsule appears to correlate with both tumor grade and stage, respectively. Detection and grading of color-coded flow within biopsy-proven cancers may identify patients with a high likelihood of biochemical relapse.
Adenocarcinoma↗
Experience with intracavernous PGE-1 in the treatment of erectile dysfunction: dose considerations and efficacy.
The recommended dose of PGE-1 as treatment for erectile dysfunction has ranged from 10-60 mcg in various studies. We conducted the present study to identify factors that influence dose tritration and maintenance. From 96 patients who presented to our institution with erectile impotence, 40 elected self injection with PGE-1. Erectile response to intracavernous injection was assessed in the course of office-based dose titration. Patients were stratified into different groups based on age and etiology of erectile dysfunction. The mean maintenance dose was calculated in each group. Patients were evaluated quarterly by physical palpation of the penis, complete blood count, serum electrolytes, and liver function tests in order to assess safety of therapy. The average maintenance dose varied with the etiology of erectile dysfunction and age of the patient. The central neurogenic group was the most responsive to PGE-1 therapy, requiring an average maintenance dosage of 5 mcg. Men with vascular etiologies required the largest maintenance dosage of 20 mcg. Furthermore, dosage requirement increased linearly with age. We conclude that dosing considerations vary widely in a clinical setting and their determination is greatly facilitated if primary and associated causes of erectile dysfunction and the age of the patient are considered.
Adolescent↗
Postcesarean analgesia with both epidural morphine and intravenous patient-controlled analgesia: neurobehavioral outcomes among nursing neonates.
UNLABELLED: Among nursing parturients after cesarean delivery, intravenous patient-controlled analgesia (PCA) with meperidine is associated with significantly more neonatal neurobehavioral depression than PCA with morphine. A single dose of epidural morphine (4 mg) decreases postcesarean opioid analgesic requirements and may reduce or prevent neonatal neurobehavioral depression associated with PCA meperidine. Prospectively, 102 term parturients underwent cesarean delivery with epidural anesthesia, 2% lidocaine and epinephrine 1:200,000. After umbilical cord clamping, each patient received epidural morphine 4 mg and was randomly allocated to receive either PCA meperidine or PCA morphine. Initial neonatal characteristics, included gestational age, Apgar scores, weight, and umbilical cord gas partial pressures. Brazelton Neonatal Behavioral Assessment Scale (NBAS) examinations were performed on each of the first 4 days of life. Nursing infants (n = 47) were grouped according to maternal PCA opioid in breast milk (meperidine [n = 24] or morphine [n = 23]); bottle-fed infants (n = 56) served as the control group. The three infant groups were equivalent with respect to initial characteristics and NBAS scores on the first 2 days of life. On the third day of life, infants in the morphine group were significantly more alert and oriented to animate human cues compared with infants in the meperidine or control group. On the fourth day of life, infants in the morphine group remained significantly more alert and oriented to animate human auditory cues than infants in the meperidine group. Average PCA opioid consumption through 48 h postpartum was equivalent (0.54 mg/kg morphine and 4.7 mg/kg meperidine); however, even with these small doses, meperidine was associated with significantly poorer neonatal alertness and orientation than morphine. Morphine is the PCA opioid of choice for postcesarean analgesia among nursing parturients. IMPLICATIONS: Among nursing parturients after cesarean delivery, intravenous patient-controlled analgesia with meperidine is associated with more neonatal neurobehavioral depression than patient-controlled analgesia with morphine. In this study, we found that nursing infants exposed to morphine were more alert and oriented to animate human cues than those exposed to meperidine.
Adult↗
Malignant eccrine spiradenoma with carcinomatous and sarcomatous elements.
A case of a 60 year old man with malignant eccrine spiradenoma involving the perineum is described. Areas of typical eccrine spiradenoma were admixed with carcinomatous and sarcomatous elements. Immunohistochemical and ultrastructural analysis revealed no evidence of epithelial differentiation in the sarcomatous areas. The tumour qualified for the designation carcinosarcoma arising in eccrine spiradenoma. The clinical course was aggressive with rapid development of nodal and pulmonary metastases.
Adenoma, Sweat Gland↗
Antiandrogen withdrawal syndrome with nilutamide.
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Androgen Antagonists↗
Current treatment of advanced prostate cancer.
Metastatic prostate cancer has been traditionally treated with androgen ablation using surgical orchiectomy or estrogens. The development of long lasting LHRH analogues has replaced these standard treatments in most patients with advanced prostate cancer. Several nonsteroidal antiandrogens are now available that may be used in combination therapy with LHRH analogues. This approach has been demonstrated in several large trials to improve the control of the disease. In spite of these advances, most men will eventually develop hormone resistance. New strategies being investigated include intermittent androgen ablation and combining initial hormonal therapy with chemotherapeutic agents. The management of hormone refractory disease remains a major clinical problem, with few standard chemotherapy agents demonstrating activity. This article reviews the principles of the current management of advanced prostate cancer and introduces some of the newer strategies under investigation.
Androgen Antagonists↗
Initial therapy of advanced prostate cancer.
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Antineoplastic Agents, Hormonal↗
Obstetric management and group B streptococcal sepsis. Have we made progress? Has it made a difference?
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Anti-Bacterial Agents↗
Color Doppler sonography of the prostate.
The digital rectal exam (DRE), serum prostate specific antigen (PSA) level and transrectal ultrasound (TRUS) serve as the primary means of early detection of prostate cancer, but all have known limitations. Because of the low predictive value for the gray scale detection of prostate cancer with TRUS, attempts have been made to improve the diagnostic accuracy of TRUS by incorporating color Doppler imaging (CDI) into the standard examination. With CDI, the sonographer has the ability to investigate both normal and abnormal flow within the prostate gland. Recent studies have supported the ability of CDI to detect vascularity in tumors that otherwise were not detectable with conventional gray scale TRUS, which suggests the potential for increase tumor detection. In the following article the rationale behind the use of color Doppler, the normal Doppler features of the prostate gland, and the result of the published studies on the diagnostic accuracy of color Doppler in prostate cancer are analyzed. In addition, areas of future research interest are reviewed.
Humans↗
Iron transport across Caco-2 cell monolayers. Effect of transferrin, lactoferrin and nitric oxide.
Differentiated Caco-2 colon carcinoma cell monolayers grown in bicameral chambers have been used as an in vitro model to study the effect of different carrier molecules on mucosal iron transport. Transfer of iron across the monolayers in the apical-to-basolateral direction was greater from ferric lactoferrin than from iron citrate, while very little transport occurred from Fe-transferrin. However, a greater proportion of iron was retained by the cells when Fe-citrate was the donor. Caco-2 cells expressed transferrin receptors (n = 1.3 x 10(5) /cell; Ka = 2 x 10(8) l/mol), but binding of lactoferrin, though substantial in quantity, had an affinity too low to measure. When monolayers were incubated with 125I-labelled lactoferrin or transferrin some 125I-activity was transported, but almost all was TCA-soluble, suggesting that degradation products rather than intact protein were being transported. Addition of 10 microM S-nitroso-N-acetyl-D,L-penicillamine (SNAP), which produces nitric oxide (NO) in solution, caused a significant increase in iron transport from ferric citrate, but not from Fe-lactoferrin or Fe-transferrin. It is concluded that in this in vitro system lactoferrin but not transferrin enhances mucosal iron transport, and that NO may play a regulatory role in iron absorption.
Biological Transport↗
A three-compartment open pharmacokinetic model can explain variable toxicities of cobra venoms and their alpha toxins.
The pharmacokinetic profiles of labelled Naja melanoleuca, Naja nivea, Naja nigricollis and Naja haje venoms and their alpha neurotoxins were determined following rapid i.v. injection into rabbits. The data obtained fitted a triexponential equation characteristic of a three-compartment open pharmacokinetic model comprising a central compartment 'blood', a rapidly equilibrating 'shallow' tissue compartment and a slowly equilibrating 'deep' tissue compartment. The distribution half-lives for the shallow compartment ranged from 3.2 to 5 min, reflecting the rapid uptake of venoms and toxins compared with 22-47 min for the deep tissue compartment denoting much slower uptake. The overall elimination half-lives, t1/2 beta, ranged from 15 to 29 hr, indicating a slow body elimination. Peak tissue concentration was reached within 15-20 min in the shallow tissue compartment. The corresponding values for the deep tissue compartment were 120 min for N. melanoleuca and N. nigricollis venoms and their toxins and 240 min for N. nivea and N. haje venoms and their toxins. Steady-state distribution between the shallow tissue compartment and the blood gave values of 0.50 and 0.92 (N. melanoleuca), 1.64 and 1.05 (N. nivea), 0.78 and 0.92 (N. nigricollis) and 1.70 and 1.03 (N. haje) for the venoms and their toxins, respectively. The corresponding values for the deep tissue compartment gave ratios of 3.31 and 3.44 (N. melanoleuca), 2.99 and 1.68 (N. nivea), 3.74 and 3.79 (N. nigricollis) and 1.39 and 2.46 (N. haje) for the venoms and their toxins, respectively. Ratios lower than unity indicate lower venom and toxin concentrations in the tissues than in the blood, while larger ratios denote higher tissue concentrations. The values thus reflect a higher affinity of the venoms and their toxins for the central than the shallow tissue compartment and for the deep tissue than the central compartment. The sites of action of the venoms seem to be located in the deep tissue compartment since most of the pharmacological, biochemical and electrocardiographic effects of the venoms started 30-60 min after i.v. injection. The mean residence time in the body, MRTb, ranged from 20.8 to 51.8 hr, which correlated well with the long duration of the pharmacological and biochemical effects induced by the venoms. The tissue distribution of the venoms and toxins was similar, with the highest uptake being in the kidneys, followed by the stomach, lungs, liver, spleen, intestine, heart and diaphragm. Very high radioactivity was found in the stomach contents, which reached values higher than the kidneys. Some of the biochemical markers were significantly changed by one or more venoms but the grouped parameters did not reflect significant changes in cardiac, renal, hepatic or electrolyte profiles as a function of time. It is concluded that antivenom, even if injected several hours after a cobra bite, is still capable of neutralizing the slowly eliminating venom. To speed up neutralization of the venom effects, doses of antivenom higher than the calculated in vitro neutralizing dose ought to be injected to compensate for the slow rate of transfer of antivenom to the tissues.
Animals↗
Real part of the heavy-ion optical potential derived from relativistic mean field theory.
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Journal Article↗
Accuracy of calculating the exchange part of the real alpha-nucleus potential.
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Journal Article↗
Characterization of isolates of Schistosoma mansoni from Egyptian villagers that tolerate high doses of praziquantel.
To determine if resistance/tolerance to the antischistosomal drug praziquantel (PZQ) is appearing in Egyptian villages within the Nile delta region, where it has been used extensively, we treated 1,607 infected villagers and observed that 321 required one additional treatment while 89 villagers required two additional treatments; 24 of the 89 were still not cured after a third dose of this drug. Eggs were isolated from fecal samples and serum was isolated from blood taken from seven villagers successfully treated after a single dose and from 14 villagers not successfully treated after two or three doses of PZQ. The eggs were used to establish infections in mice (isolates), which were then treated six weeks after infection with three different doses of PZQ. Serum was used to determine the concentration of PZQ in the infected humans. Three of the egg isolates from the 14 villagers that could not be treated with three doses of PZQ produced infections in mice that were statistically less responsive to PZQ when compared with isolates obtained from patients that were cured after a single dose of this drug. Pharmacokinetic parameters were the same in patients treated successfully after a single dose versus those not treated successfully following two or three doses, thus eliminating the possibility that poor cure rates among infected villagers was due to a decrease in PZQ bioavailability. From our data, approximately 1-2.4% of the villagers treated with PZQ could not be completely cured of their infection and three of every 1,000 treated villagers may harbor parasites that can tolerate high doses of PZQ. These results indicate that the extensive use of PZQ in the Nile delta region of Egypt has not resulted in a dramatic change in the efficacy of this drug. The isolation of schistosomes that are less susceptible to PZQ may be a warning signal that will require establishment of a monitoring system, similar to the one we have developed, to determine if the percentage of patients that cannot be cured by PZQ is increasing. Furthermore, if that percentage begins to increase over time, it will be critical to determine, by pharmacologic methods reported in this study, whether isolates obtained from uncured patients are becoming increasingly resistant to PZQ.
Adult↗
The prevalence and control of soil-transmitted nematode infections among children and women in the plantations in Sri Lanka.
OBJECTIVE: To determine the prevalence of soil-transmitted nematode infections among children and to assess the magnitude of nematode infections among women in the reproductive age group. DESIGN: Cross-sectional study. SETTING: 14 government owned plantations in the up-country and low-country regions of Sri Lanka. SUBJECTS: 1614 children 3 to 12 years of age and 246 women 18 to 44 years selected using a multi-stage random sampling technique. MEASUREMENTS: Egg count from stool samples collected from subjects using the quantitative Kato-Katz technique; percentage of children and women infected. RESULTS: 89.7% of the children and 86.2% of the women had at least one type of soil-transmitted nematode infection. Ascaris lumbricoides was the most common infection (77.0% of the children and 69.5% of the women). 69.4% of the children and 56.5% of the women had Trichuris trichiura infection and 23.2% of the children and 41.4% of the women had hookworm infection. Hookworm infection was much more common in the low country plantations. CONCLUSION: The high prevalence rates reflect widespread faecal contamination of the environment in the plantations due to poor and congested housing conditions and insufficient sanitary facilities. As the physical environment is not likely to change in the short term, the strategy for control of soil-transmitted nematode infections should focus on regular deworming of children and health education. A control program based on these principles was initiated in the estate sector after this study was completed.
Adolescent↗
The efficacy of three anthelmintic drugs given in a single dose.
OBJECTIVE: To compare the efficacy of a single dose mebendazole 500 mg from the original manufacturer and a formulation locally produced by State Pharmaceuticals Manufacturing Corporation of Sri Lanka and albendazole 400 mg in mass treatment of soil-transmitted nematode infections. DESIGN: Randomised trial. SETTING: Government owned plantations in low-country regions of Sri Lanka with poor sanitary facilities. SUBJECTS: 399 children 3 to 15 years of age infected with at least one type soil-transmitted nematode. INTERVENTION: Mebendazole 500 mg or albendazole 400 mg given as single dose treatment. MEASUREMENTS: Cure rates and egg reduction rates calculated from egg counts of pre- and post-treatment stool samples using the quantitative Kato-Katz technique. RESULTS: All three drugs were effective against Ascaris infection with cure rates above 95%. The efficacy against Trichuris trichuria was uniformly poor. For hookworm infection albendazole appeared to be more effective in a single dose with cure rates of 77.9% compared with 28.7% and 35.8% for the two mebendazole formulations; corresponding egg reduction rates were 95.4% compared with 72.0% and 74.5%. CONCLUSION: Albendazole is the drug of choice for mass deworming where hookworm disease is prominent. There was no statistically significant difference between the original and locally produced mebendazole.
Adolescent↗
Fracture of the occipital condyle: case report and review of the literature.
Fracture of the occipital condyle is a rare injury that can be easily overlooked. We report a patient with an occipital condyle fracture who presented with pyramidal syndrome and normal plain radiographs. The diagnosis was made by high-resolution computed tomographic scanning with sagittal and coronal reconstructions and magnetic resonance imaging. Surgical treatment was deferred because of spontaneous recovery. This fracture should be considered whenever a trauma patient presents neck pain and plain cervical spine radiographs show no abnormalities.
Adult↗