Diffusion-weighted MRI as a screening tool for hepatocellular carcinoma in cirrhotic livers: correlation with explant data-a pilot study.

OBJECTIVE: The purpose of this study was to compare the sensitivity and specificity of diffusion-weighted liver MRI alone with complete, multiphasic gadoteridol-enhanced MRI for the detection of hepatocellular carcinoma in cirrhotic patients before liver transplant. MATERIALS AND METHODS: This single institution retrospective study was performed after IRB approval and was HIPAA compliant. MRI scans of 37 patients who underwent liver transplant were evaluated and findings correlated with liver explant (36) or biopsy (1). All MRI scans were obtained within six months of explant. MRI from 17 patients with liver lesions by report at imaging subsequently proven to be HCC at pathology and 20 controls without liver lesions by imaging and pathology were reviewed in random order on the radiology PACS by three independent readers blinded to the MRI reports and pathology reports in two separate sittings. First, only the diffusion-weighted images (DWI) were interpreted. Second, the complete multiphasic MRI exam with DWI was reviewed. A consensus read was obtained by two separate radiologists who had access to the patients' explant data in order to map lesions. Reader-specific and pooled classification was assessed using sensitivity, specificity, positive predictive value, and negative predictive values and corresponding 95% confidence intervals (CI) for both DWI and complete MRI examination readings compared to pathology. McNemar's test and Kappa coefficient were used to assess differences (agreement) in DWI and complete examination readings. RESULTS: A total of 37 patients have been studied (25M 12F age range 21-70). Averaged results of the three independent readers demonstrated a sensitivity of 78% (95% CI 65-89%) and specificity of 88% (95% CI 77-95%) for DWI alone for detection of liver lesions, with a positive predictive value of 85% (95% CI 72-94%) and a negative predictive value of 83% (95% CI 71-91%). Review of the complete MRI exam showed a sensitivity of 90% (95% CI 76-97%) and a specificity of 82% (95% CI 66-92%) with a positive predictive value of 83% (95% CI 69-93%) and a negative predictive value of 89% (95% CI 74-97%). McNemar's agreement test revealed no significant difference between the DWI and complete multiphasic interpretations (p = 0.3458), with simple Kappa coefficient of 0.6716 (95% CI 0.5332-0.8110). Lesions identified on DWI ranged in size from 1.5 to 5 cm. Detection of lesions was decreased in the presence of artifact from motion, large ascites, and technical issues. CONCLUSION: Diffusion-weighted MRI has NPV and PPV comparable to complete multiphasic MRI examination for liver lesion detection in cirrhotic patients and may have a role in screening.

Redescription of Dracunculus globocephalus Mackin, 1927 (Nematoda: Dracunculidae), a parasite of the snapping turtle, Chelydra serpentina.

Dracunculus globocephalus Mackin, 1927 (Nematoda: Dracunculoidea) is redescribed from specimens collected from the mesentery of the snapping turtle, Chelydra serpentina (L.), in Louisiana, USA. The use of scanning electron microscopy, applied for the first time in this species, made it possible to study details in the structure of the cephalic end and the arrangement of male caudal papillae that are difficult to observe under the light microscope. This species markedly differs from all other species of Dracunculus in having the spicules greatly unequal in size and shape, in the absence of a gubernaculum, and in the disposition of male caudal papillae. The validity of D. globocephalus is confirmed, but the above mentioned morphological differences are not sufficient for listing it in a separate genus. This is the first record of D. globocephalus in Louisiana.

Quality control for parasitologic data.

Accuracy of data is of paramount concern for all research. The task of providing objective assurances of accuracy of parasitologic data for a large, multi-center epidemiologic research project in Egypt (Epidemiology 1, 2, 3 [EPI 1, 2, 3]) presented a unique set of challenges undertaken jointly by the Ministry of Health's Qalyub Center for Field and Applied Research with technical assistance from Tulane University (New Orleans, LA). The EPI 1, 2, 3 project was part of large bilateral research program, the Schistosomiasis Research Project, undertaken jointly by the governments of Egypt and the United States. This paper describes the nature of the quality control system developed to accomplish this task, presents results and discusses the findings.

PMMA bead versus parenteral treatment of Staphylococcus aureus osteomyelitis.

A. rabbit model of Staphylococcus aureus osteomyelitis was used to compare 3 weeks of clindamycin-impregnated polymethylmethacralate (PMMA) bead treatment with 3 weeks of gentamicin-impregnated polymethylmethacralate bead treatment, 4 weeks of parenteral clindamycin treatment, and surgical debridement without any antibiotic treatment. The animals were weighed throughout the course of the experiment and cortical bone and marrow flush specimens were obtained for bacterial culture at the end of therapy. The cortical specimens were bacteria free in 100% (6/6) of the animals receiving parenteral clindamycin, 83% (5/6) of the animals in the clindamycin PMMA group and, none of the animals in the gentamicin PMMA group. The marrow flush specimens were bacteria free in 83% (5/6) of the animals in the parenteral clindamycin group, 67% (4/6) of the animals in the clindamycin PMMA group, and 40% (2/5) of the animals in the gentamicin PMMA group. While these findings are preliminary and further studies with larger numbers of animals are needed, the authors suggest that when PMMA bead therapy is being contemplated, serious consideration should be given to replacing gentamicin with clindamycin in treatment of gram-positive osteomyelitis. Furthermore, incorporation of clindamycin with gentamicin (or tobramycin) should be considered when treating mixed gram-positive and gram-negative osteomyelitis.

Laboratory diagnosis of worms and miscellaneous specimens.

This article outlines the procedures to be followed when a macroscopic object thought to be a worm or other type of parasite is submitted to the clinical laboratory. These are often collected and submitted by the patient, but also may be submitted by the attending physician, the surgeon, or the pathologist. Examples of the various parasites and parasite-like objects that have been submitted to clinical laboratories are listed. Methods for preserving and examining such objects, using materials and reagents available in the clinical laboratory, are presented.

Selective retention of MPP+ within the monoaminergic systems of the primate brain following MPTP administration: an in vivo autoradiographic study.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) selectively destroys dopaminergic neurons of the substantia nigra pars compacta in humans and other primates, producing a parkinsonian condition. MPTP is metabolized to the toxin 1-methyl-4-phenylpyridine (MPP+) which is taken up by dopamine terminals. The subsequent events culminating in cell death in the substantia nigra pars compacta are not understood. To examine these events we first produced a chronic hemiparkinsonian condition in monkeys by administering a toxic dose of MPTP via the right carotid artery. One year later, these monkeys were given a trace dose of [14C]MPTP intravenously and allowed to survive 1, 3, or 10 days. In two acute conditions, monkeys were either given the radiolabeled trace dose intravenously immediately following the toxic intracarotid dose, or were given a single toxic intracarotid radiolabeled dose, and allowed to survive 1, 3, or 10 days. We show by histology and autoradiography that the chronic hemiparkinsonian condition is characterized by selective unilateral loss of nigrostriatal dopamine neurons and absence of MPP+ retention in the caudate-putamen. In the acute conditions, MPP+ is accumulated and selectively retained in high concentrations in the caudate-putamen bilaterally and throughout the nigrostriatal pathway only on the side receiving the toxic dose. In the substantia nigra pars compacta. MPP+ is accumulated in very low concentrations in the dopamine cell bodies and is not selectively retained there. At 10 days survival, the caudate-putamen on the side receiving the toxic dose loses its ability to retain MPP+. The apparent degeneration of the dopamine axon terminals in the caudate-putamen and the development of Parkinson-like behavioral signs seen at 10 days survival were observed to precede the loss of cell bodies in the substantia nigra, which appeared normal by the criteria of Nissl staining and neuromelanin content at all time points in the acute conditions. Other areas of dense MPP+ retention in all cases include noradrenergic and serotonergic cell groups and noradrenergic pathways. MPP+ in the locus coeruleus and other caudal catecholaminergic cell groups is apparently retrogradely transported there after uptake in terminal regions, and although it is retained in high concentrations, no cell loss occurs. These findings suggest that experimentally induced Parkinsonism results from molecular events initiated in the neostriatum and selectively elaborated in the nigrostriatal pathway, ultimately resulting in the death of substantia nigra pars compacta dopamine neurons. They do not support a significant role for neuromelanin binding in the toxicity of MPP+.

Cannabinoid receptor localization in brain.

[3H]CP 55,940, a radiolabeled synthetic cannabinoid, which is 10-100 times more potent in vivo than delta 9-tetrahydrocannabinol, was used to characterize and localize a specific cannabinoid receptor in brain sections. The potencies of a series of natural and synthetic cannabinoids as competitors of [3H]CP 55,940 binding correlated closely with their relative potencies in several biological assays, suggesting that the receptor characterized in our in vitro assay is the same receptor that mediates behavioral and pharmacological effects of cannabinoids, including human subjective experience. Autoradiography of cannabinoid receptors in brain sections from several mammalian species, including human, reveals a unique and conserved distribution; binding is most dense in outflow nuclei of the basal ganglia--the substantia nigra pars reticulata and globus pallidus--and in the hippocampus and cerebellum. Generally high densities in forebrain and cerebellum implicate roles for cannabinoids in cognition and movement. Sparse densities in lower brainstem areas controlling cardiovascular and respiratory functions may explain why high doses of delta 9-tetrahydrocannabinol are not lethal.

Zoonotic Onchocerca in a Japanese child.

A female Onchocerca was found in histopathological sections of a nodule removed from the foot of a 2-year-old girl in southern Japan. As in previously reported cases in Switzerland, Crimea, Canada, and the USA, evident morphological features of the worm resembled those of Onchocerca gutturosa and O. cervicalis, which are known to exist in cervical ligaments of cattle and horses, respectively, in Japan and elsewhere.

The finding of Angiostrongylus cantonensis in rats in New Orleans.

Twenty of 94 (21.4%) Rattus norvegicus trapped in New Orleans, Louisiana, between April 1986 and February 1987 were infected with Angiostrongylus cantonensis (3-62 worms per rat). This is the first report of the parasite from North America. A carnivorous snail, Euglandina rosea, was found experimentally to be able to serve as both an intermediate and a paratenic host. Other locally occurring gastropods that were successfully infected experimentally included Mesodon thyroidus, Anguispira alternata, Bradybaena similaris, Subulina octona, Polygyra triodontoides, Vaginulus ameghini, Philomycus carolinianus, Deroceras laeve, Limax flavus, and Lehmannia poirieri. Laboratory reared, 4- to 5-week-old M. thyroidus and D. laeve were able to support the development of small numbers of larvae to the third stage. First stage larvae of A. cantonensis in the feces of experimentally infected rats were found not to migrate out of the fecal pellet; this behavior favors the infection of feces-consuming gastropods. Twenty heavily infected L. flavus were observed over a period of 2 months, and shedding of third stage larvae of A. cantonensis was never seen. While factors support the spread of A. cantonensis in rats in the southern United States, the probability of human infection is uncertain since the parasite is transmitted primarily by ingestion of raw intermediate and paratenic hosts.

Granulinema gen. n. a new dracunculoid genus with two new species (G. carcharhini sp. n. and G. simile sp. n.) from the bull shark, Carcharhinus leucas (Valenciennes), from Louisiana, USA.

Two new species of dracunculoid nematodes, G. carcharhini sp. n. and G. simile sp. n., representing a new genus Granulinema gen. n. (Dracunculoidea: Micropleuridae) are described from the bull shark, Carcharhinus leucas, from Louisiana (Lake Borgne), USA; the site of their localization in the host is unknown (probably abdominal cavity). The nematodes of both species were found in tissue juice and only males, juvenile females and body fragments of more advanced but nongravid females were obtained. Granulinema gen. n. differs from Micropleura, the only other genus in the family Micropleuridae, mainly by the presence of marked, dark excretory corpuscles in lateral excretory canals, pointed tail in females, greater number (6) of postanal pairs of caudal papillae in males, and by the presence of conspicuous transverse cuticular ornamentations on the body surface of mature females. The two new species can be easily distinguished from each other by the length of their spicules (0.78-0.90 mm in G. carcharhini sp. n. and 0.20-0.36 mm in G. simile sp. n.); moreover, there are two pairs of preanal papillae in the male of G. carcharhini sp. n., while there are three pairs in G. simile sp. n.

The clinical and immunologic responses of normal human volunteers to low dose hookworm (Necator americanus) infection.

Five normal human volunteers were exposed to approximately 50 infective larvae of Necator americanus and were observed for the development of clinical signs or symptoms and for changes in blood eosinophil levels, IgG antibody titers, total and parasite-specific IgE, and lymphocyte blastogenic responses for 6-10 weeks. Bronchoalveolar lavage was performed on four subjects prior to infection and at times when larval migration through the pulmonary tree was likely. Eggs were demonstrated in the stools of four volunteers who remained untreated for more than 6 weeks; one volunteer had to be treated at day 40 because of severe gastrointestinal symptoms. All others also complained of abdominal pain and flatulence between days 35-40. All volunteers developed marked blood eosinophilia which peaked between days 38-64 and ranged from 1,350-3,828 eosinophils/mm3. Small increases in total and parasite-specific IgE and IgG were noted in some volunteers. One volunteer showed a significant lymphocyte blastogenic response. With the exception of mucosal erythema, bronchoalveolar lavage results were unremarkable. Our data indicate that a single small inoculum of hookworm larvae is capable of producing significant transient gastrointestinal morbidity and marked blood eosinophilia but does not induce other prominent T cell- and B cell-dependent immune responses.

Larvicidal activity of albendazole against Necator americanus in human volunteers.

This study evaluated the efficacy and tolerance of a single oral 400-mg dose of albendazole on Necator americanus larvae, and compared its efficacy when administered between meals or with a meal. Twenty-nine healthy and hookworm-free male volunteers were exposed on the forearm to approximately 45 8-day-old N. americanus larvae. All subjects developed discrete maculopapular eruptions at the site of larval application. Following a random double-blind study design, each subject received at the end of the 6th post-infection day either the investigational drug or a placebo as follows: Group I (n = 8)-placebo; Group II (n = 11)-400 mg albendazole with a meal; Group III (n = 10)-400 mg albendazole 3 or more hours after or before a meal. On day 56 post-infection, the stools of all subjects who received placebo were positive for N. americanus eggs (by zinc sulfate flotation technique), compared with 48% positivity (10/21) in those who received albendazole (P = 0.01). By day 63 post-infection, an additional three subjects in the treatment group became positive, for an overall 62% rate of positivity (13/21), i.e., albendazole prevented patent infection in 38%. Administration of albendazole with a meal did not alter drug efficacy. In those subjects in whom patent infections were not prevented, egg output was one-fourth that of the placebo group. There was no difference in viability of eggs appearing in feces of treated and untreated subjects as judged by larval development in Harada-Mori cultures. Our data indicate that albendazole is active against pre-intestinal stages of N. americanus in human infections.

Two cases of human Lagochilascaris infection in Colombia.

Two human cases of infection with Lagochilascaris are described from Colombia. One patient was a 21 year-old woman who suffered from repeated attacks of tonsillitis and passage of worms from the nose. When a tonsillectomy was performed, numerous worms were found in the tissues. Treatment with thiabendazole and mebendazole was ineffective. She was cured after treatment with levamisole. The second patient was a 7 year-old girl who had a painful abscess on the neck that contained adult worms. She was also cured of this infection after treatment with levamisole. These are the first cases described from Colombia, and bring the total number of human cases recorded to twenty-three.

Ancylostoma larva in a muscle fiber of man following cutaneous larva migrans.

This is a report of a case of massive cutaneous larva migrans in a 20-year-old man who also had pulmonary symptoms and larval invasion of the skeletal muscles. In sections of a muscle biopsy specimen taken 3 months after the initial cutaneous lesions, a third-stage Ancylostoma larva, probably A. caninum, was found within a muscle fiber.

Life cycle and development of Lagochilascaris sprenti (Nematoda: ascarididae) from opossums (Marsupialia: didelphidae) in Louisiana.

The life cycle of Lagochilascaris sprenti, a species which occurs in the stomach of opossums (Didelphis virginiana) in Louisiana, was determined. The larva in the egg developed to the infective stage after eggs from the feces of infected animals were in culture about 30 days. When eggs containing infective larvae were fed to mice, the larvae hatched, penetrated the intestinal mucosa, migrated through the liver and lungs, and eventually reached the skeletal muscles where they became encapsulated. Larvae were also found encapsulated in the skeletal muscles of rats, gerbils, hamsters, monkeys, and a rabbit fed infective eggs. No larvae were found in the muscles of opossums fed infective eggs. However, when opossums were fed mice with 39- to 204-day-old Lagochilascaris infections, larvae developed in the gastric mucosa to the adult stage within 21 days. Adult worms inhabited cavities in the submucosa of the stomach from which they could migrate through openings into the lumen. One to three abscesses, each containing a single adult worm, were found in the musculature of 16.4% of the mice fed infective eggs.