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Biomedical subjects

D R Brooks

Publications and source records attributed to D R Brooks.

At least 19 recordsLinked to original sources

Limitations and late complications of third-generation automatic cardioverter-defibrillators.

BACKGROUND: This study examines the limitations and complex management problems associated with the use of tiered-therapy, implantable cardioverter-defibrillators (ICDs). METHODS AND RESULTS: The study group comprises the first 154 patients undergoing implantation of tiered-therapy ICDs at our institution. Pulse generators from three different manufacturers were used. In 39 patients, a complete nonthoracotomy lead system was used. The perioperative mortality was 1.3%. Of these 154 patients, 37% experienced late postoperative problems. Twenty-one patients required system revision within 36.5 months (mean, 8.57 +/- 11.3) of surgery. Reasons for revision were spurious shocks due to electrode fractures (3) or electrode adapter malfunction (2), inadequate signal from endocardial rate-sensing electrodes (3), superior vena cava or right ventricular coil migration (5), failure to correct tachyarrhythmias due to a postimplant rise in defibrillation threshold (5), or pulse generator failure (3). One of these patients required system removal for infection after revision of an endocardial lead. A further 32 patients received inappropriate shocks for atrial fibrillation with a rapid ventricular response or sinus tachycardia. Two of these patients also received shocks for ventricular tachycardia initiated by antitachycardia pacing triggered by atrial fibrillation. Ventricular pacing for bradycardia was associated with inappropriate shocks due to excessive autogain in 2 patients. CONCLUSIONS: Despite the major diagnostic and therapeutic advantages of tiered-therapy ICDs, a significant proportion of patients continue to experience hardware-related complications or receive inappropriate shocks.

Algorithms

A mutation-specific PCR system to detect sequence variation in the dihydropteroate synthetase gene of Plasmodium falciparum.

Sulphur-based antimalarial drugs targeted at dihydropteroate synthetase (DHPS) are frequently used in synergistic combination with inhibitors of dihydrofolate reductase (DHFR) to combat chloroquine-resistant malaria. We have previously shown that lines of Plasmodium falciparum resistant to the most commonly used sulpha drug, sulphadoxine, carry point mutations in the DHPS coding region, relative to the sequence of sensitive strains (Brooks et al., Eur. J. Biochem. 224 (1994) 397-405). We have now developed PCR diagnostic assays based on allele-specific amplification that are able to detect such mutations. The four tests described can reliably discriminate all of the mutations observed to alter codons 436, 581 and 613, yielding allele-specific amplification products of different sizes in each case. Moreover, by careful adjustment of primer length and the degree of mismatch to target and non-target alleles, we were able to standardise all four tests to a single set of PCR conditions, allowing all possible mutations to be monitored simultaneously on one thermocycler. These assays should prove invaluable in further assessing the contribution of specific base changes in the DHPS gene of the parasite to the sulphadoxine resistance phenotype and to the clinical failure of the sulphadoxine/pyrimethamine combination Fansidar.

Alleles

Proteocephalus chamelensis n. sp. (Cestoda: Proteocephalidae) from the "guavina" Gobiomorus maculatus (Osteichthyes: Eleotrididae) in Chamela Bay, Jalisco, México.

A new species of Proteocephalus inhabiting the eleotridid estuarine fish Gobiomorus maculatus is described from Chamela Bay, Jalisco State, Mexico. The new species and P. pugetensis are nearly identical in strobila length, presence of a vestigial apical organ, having vaginae only anterior to the cirrus sac, an average of 4-7 uterine diverticula per proglottis, and a ratio of cirrus sac length to proglottis width averaging approximately 1:4. Proteocephalus pugetensis differs from the new species by having an average of 35 rather than 68 testes per proglottis, vitelline follicles terminating posteriorly at the level of the anterior margin of the ovary rather than at the level of the posterior margin, and equatorial genital pores rather than genital pores located in the anterior 1/4 of the proglottis. Finally, Proteocephalus pugetensis occurs from estuarine habitats along the Pacific coast of the United States; the new species was collected from an estuarine habitat on the Pacific coast of México.

Animals

Acanthobothrium nicoyaense n. sp. (Eucestoda: Tetraphyllidea: Onchobothriidae) in Aetobatus narinari (Euphrasen) (Chondrichthyes: Myliobatiformes: Myliobatidae) from the Gulf of Nicoya, Costa Rica.

A new species of Acanthobothrium in Aetobatus narinari from the Gulf of Nicoya, Costa Rica, most closely resembles Acanthobothrium colombianum in the same host and A. urotrygoni in Urotrygon venezuelae from Cartagena, Colombia, by having relatively few proglottides per strobila, spinose cephalic peduncles, bothridial margins free at their posterior ends, and irregularly shaped rather than spherical or elongate cirrus sacs. Acanthobothrium colombianum differs from the new species by being as much as 35 mm rather than no more than 4.7 mm long and by having 31-48 rather than 13-19 proglottides, an average of 46 rather than 15 testes per proglottis, and bothridial hooks averaging 185 microns rather than 137 microns in total length. Acanthobothrium urotrygoni differs from the new species by being as much as 15 mm rather than no more than 4.7 mm long and by having V-shaped rather than H-shaped ovaries, bothridial hooks averaging 95 microns rather than 137 microns in total length, by having an average of 28 rather than 15 testes per proglottis, and by having poral ovarian arms extending anteriorly to the posterior margin of the cirrus sac and aporal arms extending to the lateral margin of the cirrus sac.

Animals

Phylogenetic relationships of the genera of the Pronocephalidae Looss, 1902 (Digenea: Paramphistomiformes).

Quantitative phylogenetic analysis of 20 nominal genera of the Pronocephalidae based on 47 morphological transformation series produced 6 equally parsimonious trees, each with a consistency index of 77.8%. All trees agree that Adenogaster is the sister group to the rest of the pronocephalids, and a new subfamily is proposed for it. The Pronocephalinae comprises Pronocephalus, Ruicephalus, Neopronocephalus, Macravestibulum, Choanophorus, Cetiosaccus, and Metacetabulum. The Charaxicephalinae comprises Charaxicephalus, Desmogonius, Diaschistorchis, Pleurogonius, Iguanacola, Renigonius, Parapleurogonius, Himasomum, Pyelosomum, Cricocephalus, Barisomum, and Pseudobarisomum. An amended diagnosis for Himasomum is presented. The trees differ only in the placements of Pleurogonius, Renigonius + Parapleurogonius, Iguanacola, and Himasomum relative to each other. Parapronocephalum and Notocotyloides are members of the clade containing the Notocotylidae. The phylogenetic tree supports interpretations of 3-4 transitions from marine to freshwater turtles, 3 host switches from marine turtles to the Galapagos marine iguana and 3 from marine turtles to the French angelfish, and widespread host switching among marine chelonians. No switches to non-chelonian hosts coincide with transitions from marine to freshwater.

Animals

Phylogenetic relationships among the species of Pyelosomum Looss, 1899 (Digenea: Pronocephalidae).

Comparative morphological study of 10 nominal species of pronocephalids forming a clade diagnosed by plump rounded bodies, sinuous ceca, and short esophagi supports the recognition of 7 species, with Pyelosomum longicaecum a junior synonym of P. renicapite, and P. solum and Myosaccus chelonei species incertae sedis. Phylogenetic analysis of the 7 recognized species, based on 18 morphological transformation series, produced a single tree with a consistency index of 86%. That tree suggests that Pyelosomum is paraphyletic unless Astrorchis, Epibathra, and Myosaccus are included in it. Accordingly, all are considered junior synonyms of Pyelosomum. Epibathra stenobursata is designated Pyelosomum stenobursata comb. n.

Animals

Serendip deborahae n. gen. and n. sp. (Eucestoda: Tetraphyllidea: Serendipidae n. fam.) in Rhinoptera steindachneri Evermann and Jenkins, 1891 (Chondrichthyes: Myliobatiformes: Myliobatidae) from southeastern Ecuador.

Cestodes collected in spiral valves of Rhinoptera steindachneri from the southern coast of Ecuador represent an undescribed species of Tetraphyllidea. The new species has bothridia possessing septa but lacking apical suckers. It is diagnosably distinct from all other tetraphyllidean genera by possessing a scolex comprising 4 triangular bothridia that are fused together forming a platelike structure, each of which is subdivided by 2 simple and 1 bifurcating septa radiating from its base and ringed by marginal loculi; therefore, a new genus is proposed for it. By exhibiting some degree of bothridial fusion, testes arranged in 2 layers in the proglottis and postovarian testes, the new species appears to be a member of a clade containing Dioecotaenia, Duplicibothrium, and Glyphobothrium. The new species possesses vitelline fields that converge dorsally in each proglottis, except for the ovarian and terminal genitalia areas, a feature that has been reported previously only in Duplicibothrium and Glyphobothrium. Furthermore, Duplicibothrium and Glyphobothrium, like the new species, are markedly protandric. Therefore, we propose that Duplicibothrium, Glyphobothrium, and the new species comprise the sister group of the Dioecotaeniidae, and propose a new family name for the clade. Tritaphros is rejected as a possible sister group for the clade; suggested alternatives include some species of Caulobothrium, Rhodobothrium, or some members of the Phyllobothrium centrurum group.

Animals

Sequence variation of the hydroxymethyldihydropterin pyrophosphokinase: dihydropteroate synthase gene in lines of the human malaria parasite, Plasmodium falciparum, with differing resistance to sulfadoxine.

Dihydropteroate synthase (H2Pte synthase) is the target of the sulfur-based antimalarial drugs, which are frequently used in synergistic combination with inhibitors of dihydrofolate reductase (H2folate reductase) to combat chloroquine-resistant malaria. We have isolated the H2Pte synthase coding sequence of the most pathogenic human parasite Plasmodium falciparum. It forms part of a longer coding sequence, located on chromosome 8, that also specifies 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase (CH2OH-H2pterinPP kinase) at its 5' proximal end. This domain is unusually large, with two long insertions relative to other CH2OH-H2pterinPP kinase molecules. To investigate a possible genetic basis for clinical resistance to sulfa drugs, we sequenced the complete H2Pte synthase domains from eleven isolates of P. falciparum with diverse geographical origins and levels of sulfadoxine resistance. Overall, point mutations in five positions were observed, affecting four codons. Parasite lines exhibiting high-level resistance were found to carry either a double mutation, altering both Ser436 and Ala613, or a single mutation affecting Ala581. The mutations at positions 436 and 581 have the same location relative to each of two degenerate repeated amino acid motifs that are conserved across all other known H2Pte synthase molecules. The amino acid alteration at residue 613 is identically positioned relative to a different conserved motif. The fourth amino acid residue (437) affected by mutation, though adjacent to the apparently crucial residue 436, shows no obvious correlation with resistance. Although these mutations have no exact counterparts in any other organism, that at position 581 falls within a region of three amino acids where H2Pte synthase is modified in various ways in a number of sulfonamide-resistant pathogenic bacteria. Copy-number analysis indicated that there was no amplification of the H2Pte synthase domain in resistant parasite lines of P. falciparum, compared to sensitive lines.

Amino Acid Sequence

Elevated blood lead levels among construction workers in the Massachusetts Occupational Lead Registry.

Although the construction industry until recently was exempt from the Occupational Health and Safety Administration General Industry Lead Standard, including its medical monitoring provisions, periodic blood lead tests have been required for residential "deleaders" and structural painters in Massachusetts. Sixty-three percent of the 381 registrants in the Massachusetts Occupational Lead Registry with blood lead levels of 1.93 mumol/L or higher are construction workers. This proportion is much higher than that reported by registries of several states selected for comparison. These data highlight the need for better protection from lead exposure and the effectiveness of mandatory medical surveillance in identifying elevated blood lead levels among construction workers.

Adolescent

Escherbothrium molinae n. gen. et n. sp. (Eucestoda: Tetraphyllidea: Triloculariidae) in Urotrygon chilensis (Chondrichthyes: Myliobatiformes: Urolophidae) from the Gulf of Nicoya, Costa Rica.

Cestodes collected in spiral valves of the stingray Urotrygon chilensis from the Pacific coast of Costa Rica represent an undescribed species of Tetraphyllidea. By possessing more than 2 loculi as well as an apical sucker on each bothridium, the new species is diagnosably distinct from all other tetraphyllidean genera; therefore, a new genus is proposed for it. The new species also possesses globular structures irregularly arranged on the surface of the bothridia. We found similar structures on the bothridial faces of Trilocularia acanthiaevulgaris, possibly indicating phylogenetic relationships with the new species. This possibility is enhanced by the observation that the bothridia of T. acanthiaevulgaris comprise 2 loculi and an apical sucker, rather than 3 loculi.

Animals

Occupation, smoking, and the risk of high-grade invasive bladder cancer in Missouri.

Numerous epidemiological studies have established that occupational exposures and smoking are the two major known risk factors for the development of bladder cancer. Using data from the Missouri Cancer Registry, we investigated the hypothesis that individuals with occupationally-related bladder cancer are more likely to have a more invasive form of the disease. Data were analyzed for 2,893 white males diagnosed with primary bladder cancer in Missouri between 1984 and 1988. Of the 1,415 cases whose occupational status was recorded, 236 (17%) were employed in high-risk occupations. Cases with high-grade disease were more likely to have been employed in a high-risk occupation, after adjustment for age and smoking (adjusted odds ratio [AOR] = 1.7, 95% confidence interval [CI] = 1.1-2.6). High-risk workers under 60 years of age were most at risk for developing high-grade bladder tumors (AOR = 2.3, 95% CI = 1.0-5.3). There was no overall association between high-risk occupation and late-stage disease (AOR = 1.1, 95% CI = 0.7-1.5), but it was present in the men younger than 60 years of age (AOR = 2.0, 95% CI = 1.0-3.8). No association was found between tobacco use and grade (AOR = 1.1, 95% CI = 0.8-1.5), but cases with late-stage disease were more likely to be smokers (AOR = 1.5, 95% CI = 1.1-1.9). When occupations were examined individually, motor vehicle operators, truck drivers, vehicle mechanics, other mechanics, and janitors were among those most likely to be diagnosed with high-grade or late-stage tumors. Although further studies are necessary to confirm these results, they suggest that surveillance and targeted screening of workers in high-risk occupations may result in a greater yield of early invasive cancers and possibly decrease the mortality associated with this disease.

Aged

Cestode parasites in Potamotrygon motoro (Natterer) (Chondrichthyes: Potamotrygonidae) from southwestern Brazil, including Rhinebothroides mclennanae n. sp. (Tetraphyllidea: Phyllobothriidae), and a revised host-parasite checklist for helminths inhabiting neotropical freshwater stingrays.

Specimens of 5 species of cestodes were collected in 6 specimens of the freshwater stingray species Potamotrygon motoro (Natterer), collected in the vicinity of Corumba, Mato Grosso do Sul, Brazil. Acanthobothrium regoi, Potamotrygonocestus orinocoensis, Rhinebothroides venezuelensis, and Rhinebothrium paratrygoni are reported from P. motoro and from southwestern Brazil for the first time. Rhinebothroides mclennanae n. sp. appears to be the sister species of Rhinebothroides glandularis, the only other member of the genus exhibiting darkly staining glandular cells lying free in the parenchyma surrounding the terminal genitalia. The new species resembles Rhinebothroides glandularis, Rhinebothroides freitasi, and Rhinebothroides scorzai by having poral ovarian arms that extend anteriorly beyond the posterior margin of the cirrus sac, coiled vaginae, and vitelline follicles not interrupted on the poral side in the vicinity of the genital pore. It differs from all 6 previously described members of the genus by possessing an average of 31 testes per proglottid, compared with an average of 45 for R. glandularis, 55 for R. freitasi and R. venezuelensis, 77 for Rhinebothroides circularisi and Rhinebothroides moralarai, and 80 for R. scorzai. An updated phylogenetic tree for Rhinebothroides is presented.

Animals

Origins, diversification, and historical structure of the helminth fauna inhabiting neotropical freshwater stingrays (Potamotrygonidae).

Members of the freshwater stingray family Potamotrygonidae occur throughout the major river systems of eastern South America that empty into the Atlantic Ocean. Ichthyologists have tended to assume that the ancestor of the potamotrygonids was an Atlantic marine or euryhaline stingray that dispersed into freshwater, presumably during the last marine ingression 3-5 million years ago. The helminth parasites that inhabit potamotrygonids suggest an alternative perspective on their origin. Phylogenetic and biogeographic analysis of the helminths inhabiting potamotrygonids suggest that the hosts are derived from an ancestral Pacific urolophid stingray that was trapped in freshwater by the uplifting of the Andes beginning perhaps as early as the early Cretaceous period and ending by the mid-Miocene epoch, changing the course of the Amazon River, which previously had flowed into the Pacific Ocean.

Animals

Parasites and sexual selection: a macroevolutionary perspective.

The Hamilton-Zuk hypothesis postulates a causal link between parasitism and the evolution of epigamic traits by intersexual selection. Oversimplified assumptions about basic parasite biology, ambiguous formulation of the hypothesis, and poor communication between ethologists and parasitologists have hampered its testing. The hypothesis is supported at the microevolutionary level if females show significant preference for lightly or uninfected males, if intensity of infection reflects host resistance to parasites that depress host fitness by causing disease, and if intensity of infection is related to the degree of epigamic development. It must be shown that particular parasites cause disease, that the host population is polymorphic for resistance to infection by those species, and that female hosts are capable of distinguishing male hosts with low parasite loads due to heritable aspects of host resistance from males that are uninfected due to chance. The macroevolutionary prediction of the hypothesis, that species displaying strongly developed epigamic characters should host "more parasites" than species with weakly developed epigamic traits, contradicts the microevolutionary dynamic of the hypothesis, and is too ambiguous. We propose a macroevolutionary prediction based on understanding the evolutionary origin of epigamic traits and the evolutionary origin of each host-parasite association. Associations originating in the ancestor in which the epigamic trait appeared corroborate the hypothesis most strongly; those originating prior to the evolution of the epigamic trait corroborate it weakly; those beginning after the origin of the epigamic trait could not have been involved in the origin and spread of the epigamic trait.

Animals