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Biomedical subjects

T A Klein

Publications and source records attributed to T A Klein.

At least 37 records · Page 2Linked to original sources

Prevention of sporogony of Plasmodium falciparum and P. berghei in Anopheles stephensi mosquitoes by transmission-blocking antimalarials.

The sporontocidal activity of three 8-aminoquinolines, a 1,4-naphthoquinone, and three dihydroacridine-diones was determined against the ANKA clone of Plasmodium berghei and both chloroquine-sensitive (NF54) and chloroquine-resistant (7G8) P. falciparum. Anopheles stephensi mosquitoes previously fed on P. berghei--infected mice or P. falciparum--infected cultures were refed on uninfected mice treated previously with a given drug. Sporontocidal activity was determined by assessing both oocyst and sporozoite development. Neither primaquine nor menoctone exhibited sporontocidal activity against P. berghei or either strain of P. falciparum at a dose of 100 mg base drug/kg mouse body weight, whereas the other five compounds each effectively interrupted the sporogonic development of all three parasite strains at this dose. These data clearly demonstrate that experimental dihydroacridine-diones and 8-aminoquinolines are capable of interrupting the sporogonic development of P. berghei and chloroquine-sensitive and chloroquine-resistant P. falciparum. These data also suggest that the P. berghei model may be used to accurately predict sporontocidal activity against P. falciparum.

Animals↗

The effect of a surgical lubricant on in vivo sperm penetration of cervical mucus.

The implications of these data is that coital lubricants may impair fertility of some couples. Unfortunately, conception was not an end point on this study, and our conclusions must be considered inferential. Nevertheless, the results from this study lead us to recommend avoidance of surgical lubricants by couples attempting pregnancy.

Adult↗

Genetic evidence for the existence of cryptic species in the Anopheles albitarsis complex in Brazil: allozymes and mitochondrial DNA restriction fragment length polymorphisms.

Allozyme and mitochondrial DNA (mtDNA) restriction studies were undertaken to determine the extent of genetic divergence among field populations of Anopheles albitarsis in Brazil. Two sympatric species, An. deaneorum and An. marajoara, were identified in collections from Costa Marques (CM), Rondonia. Genetic evidence includes (1) the presence of two types of individuals, each with diagnostic allelic clusters (for Had-1, Pgi-1, Pep-1, Mpi-1, and Idh-1), (2) a deficiency of heterozygotes, and (3) characteristic mtDNA haplotypes. In addition, two allopatric cryptic species of An. marajoara were identified, one from Iguape (An. marajoara form IG), Sao Paulo state, and the other from the Island of Marajo (An. marajoara form MA). Though form IG and form-MA resemble form CM in wing spot morphology, they differ from it in diagnostic allozymes and mtDNA haplotypes. An. marajoara form CM had a higher variability (mean heterozygosity, H = 0.22, and percentage of polymorphic loci, P = 66.7) than did form IG and form MA (H = 0.08 in both, and P = 25.0 and 33.3, respectively). Form MA and form IG are genetically more similar to each other than both are to form CM. Based on wing morphology, estimates of F statistics, and genetic similarities, we propose that An. albitarsis in Brazil is a species complex. It comprises at least two morphologically distinguishable species: (1) An. deaneorum (currently one taxon) and (2) the An. marajoara species complex, which further consists of at least three cryptic forms, marajoara form MA, marajoara form IG, and marajoara form CM.

Alleles↗

Random amplified polymorphic DNA (RAPD) markers readily distinguish cryptic mosquito species (Diptera: Culicidae: Anopheles).

The usefulness of random amplified polymorphic DNA (RAPD) was examined as a potential tool to differentiate cryptic mosquito species. It proved to be a quick, effective means of finding genetic markers to separate two laboratory populations of morphologically indistinguishable African malaria vectors, Anopheles gambiae and An. arabiensis. In an initial screening of fifty-seven RAPD primers, 377 bands were produced, 295 of which differed between the two species. Based on criteria of interpretability, simplicity and reproducibility, thirteen primers were chosen for further screening using DNA from thirty individuals of each species. Seven primers produced diagnostic bands, five of which are described here. Some problematic characteristics of RAPD banding patterns are discussed and approaches to overcome these are suggested.

Animals↗

The predictive value of hysterosalpingography for tubal and peritoneal infertility factors.

OBJECTIVE: To investigate a practical classification system of hysterosalpingogram (HSG) results that accurately identifies patients with severe pelvic disease or a normal pelvis to allow appropriate patient counseling of therapeutic options. DESIGN: Retrospective chart review from university teaching hospital. Hysterosalpingography results were classified as normal, abnormal (bilateral distal tubal obstruction), or suspicious (all others). At surgery, chromopertubation was performed, and pelvic disease was documented. RESULTS: From a total of 756 patients, HSGs were confirmed surgically in 96.6% of normals, 63.1% of suspicious, and 95.7% of abnormal. Associated moderate-severe pelvic disease was found in 16.2% of normals, 53.9% of suspicious, and 81.7% of abnormal. CONCLUSION: Abnormal HSGs are highly predictive of severe pelvic disease, and counseling of treatment options does not require diagnostic laparoscopy. Patients with suspicious HSGs frequently have normal tubes but also have a significant likelihood of tubal or associated pelvic disease, and they are responsible for the poor predictive value of the HSG. This group of patients requires confirmatory laparoscopy preferably by a physician qualified in pelviscopic surgery. Normal HSGs have a high negative predictive value. Nevertheless, the incidence of associated pelvic disease in the normal HSG group is high enough to warrant diagnostic laparoscopy if nonsurgical treatment is unsuccessful.

Fallopian Tube Diseases↗

Natural killer cell activity from pregnant subjects is modulated by RU 486.

Natural killer cells form an integral component of the body's innate immune system. Natural killer cell activity is reduced during pregnancy, especially in the latter half. To investigate the role progesterone may play in immunomodulating natural killer cell activity during pregnancy, we evaluated the effect of RU 486 on natural killer cells isolated from pregnant subjects. Natural killer cell activity was measured with an 18-hour, Chromium 51 release, microcytotoxicity assay with K-562 cells as target cells. We demonstrated that RU 486, in a concentration range from 5 to 40 mumol/L, augmented natural killer activity threefold to fivefold over baseline. This augmentation of activity was suppressed to baseline by the addition of excess progesterone. The addition of hydrocortisone resulted in an insignificant reduction in this augmented activity. This study suggests that progesterone may play a role as an immunomodulating factor in maternal acceptance of the fetal allograft.

Adolescent↗

Vector incrimination and effects of antimalarial drugs on malaria transmission and control in the Amazon basin of Brazil.

World ecosystems differ significantly and a multidisciplinary malaria control approach must be adjusted to meet these requirements. These include a comprehensive understanding of the malaria vectors, their behavior, seasonal distribution and abundance, susceptibility to insecticides (physiological and behavioral), methods to reduce the numbers of human gametocyte carriers through effective health care systems and antimalarial drug treatment, urban malaria transmission versus rural or forest malaria transmission, and the impact of vaccine development. Many malaria vectors are members of species complexes and individual relationships to malaria transmission, seasonal distribution, biting behavior, etc. is poorly understood. Additionally, malaria patients are not examined for circulating gametocytes and both falciparum and vivax malaria patients may be highly infective to mosquitoes after treatment with currently used antimalarial drugs. Studies on the physiological and behavioral effects of DDT and other insecticides are inconclusive and need to be evaluated.

Animals↗

Comparative susceptibility of anopheline mosquitoes to Plasmodium falciparum in Rondonia, Brazil.

Five anopheline species, Anopheles deaneorum, An. albitarsis, An. triannulatus, An. oswaldoi, and An. mediopunctatus were compared to An. darlingi for susceptibility to infection by P. falciparum in Costa Marques, Rondonia, Brazil. Laboratory reared F1 An. darlingi and anopheline test species were allowed to feed at the same time on falciparum malaria patients who had gametocytes in their blood, and who had not yet been treated with quinine. Mosquitoes were dissected and examined for oocysts on day 9, and for sporozoites on days 16-20 after feeding. Anopheles mediopunctatus had higher mean numbers of oocysts and oocyst positive rates than An. darlingi. The oocyst positive rate and the mean number of oocysts in An. deaneorum and An. darlingi were similar. Anopheles triannulatus and An. oswaldoi had fewer oocysts than An. darlingi. The salivary gland sporozoite infection rate was similar for An. mediopunctatus and An. deaneorum and much lower for An. triannulatus and An. oswaldoi when compared to An. darlingi. Anopheles albitarsis developed oocysts, but sporozoites did not invade the salivary glands. In relative levels of susceptibility to P. falciparum, An. darlingi was equal to An. mediopunctatus which was greater than An. deaneorum, which was greater than An. triannulatus, which was greater than An. oswaldoi.

Animals↗

Infection of Anopheles darlingi fed on patients with Plasmodium falciparum before and after treatment with quinine or quinine plus tetracycline.

Anopheles darlingi fed on eight falciparum malaria patients with gametocytes before and after treatment with quinine sulfate or quinine sulfate plus tetracycline became infected. Quinine and quinine plus tetracycline had no apparent sporontocidal or gametocytocidal effect on late stage immature and mature gametocytes. Plasmodium falciparum gametocytes are persistent and infected mosquitoes for up to 21 days after patients were treated with quinine plus tetracycline. Sporogonic development was similar for groups of mosquitoes fed before and after patients were treated with these schizontocides. The percentages of infected mosquitoes that developed salivary gland infections were also similar for groups of mosquitoes fed before and after treatment. Twenty-four hours after treatment with 45 mg of primaquine phosphate, falciparum malaria patients were not infective to An. darlingi.

Animals↗

Comparative susceptibility of anopheline mosquitoes in Rondonia, Brazil to infection by Plasmodium vivax.

Seven anopheline species from Costa Marques, Rondonia, Brazil were compared with Anopheles darlingi for susceptibility to infection by Plasmodium vivax. Laboratory-reared F1 progeny of field-collected An. darlingi and the test anopheline species were fed at the same time on the same patients, all of whom had gametocytes in peripheral blood before treatment. Mosquitoes were dissected on day 8 after infection for oocysts and on days 14-16 after infection for sporozoites. The mean numbers of P. vivax oocysts and the percent of salivary gland infections for An. darlingi and An. deaneorum were similar and far exceeded those found in the other anopheline species tested. Anopheles albitarsis and An. mediopunctatus were less susceptible to infection by oocyst measurements than An. darlingi. However, for oocyst-infected An. albitarsis and An. mediopunctatus, the percent of mosquitoes with salivary gland infections and the numbers of sporozoites in the salivary glands were similar to An. darlingi. Anopheles triannulatus and An. oswaldoi were both susceptible to P. vivax infection, but the sporozoite infection rates and the numbers of sporozoites observed in the salivary glands were very low. Anopheles braziliensis and An. benarrochi both developed oocysts, but were never observed to have sporozoites in the salivary glands. These studies implicate some anopheline species as potential malaria vectors, but also show that species previously incriminated by ELISA techniques are not vectors of malaria parasites in Costa Marques, Rondonia, Brazil.

Animals↗

Infection of Anopheles darlingi fed on patients infected with Plasmodium vivax before and during treatment with chloroquine in Costa Marques, Rondonia, Brazil.

Patients with asexual and sexual parasites of Plasmodium vivax were treated orally with 600 mg of chloroquine diphosphate at hour zero, followed by 300 mg at 8, 24 and 48 hr. Anopheles darlingi were fed before the first dose (-0.5 hr) and at 0.5, 1, 2, 4, 6, 8, 9, 10, 11, 12, 20, 24, 36, 48, 60, and 72 hr later. Mosquitoes were examined for oocysts on day 8 and sporozoites on day 15 after infection. The frequency of infected mosquitoes and the mean number of oocysts were lower in mosquitoes that fed on patients 2-4 hr after the initial dose of chloroquine than in mosquitoes fed before treatment and at 0.5 and 1 hr. This sporontocidal effect was temporary, since the frequency of infected mosquitoes and the mean number of oocysts increased in mosquitoes fed 4-8 hr after the first dose. Nearly all mosquitoes fed on patients after the third dose of chloroquine, at 24 hr, were negative for P. vivax oocysts. Oocysts in mosquitoes fed on patients before, during, and after chloroquine treatment appeared normal and produced sporozoites. We conclude that chloroquine affects either the gametocytes, fertilization, zygotes, and/or ookinetes of P. vivax, but not subsequent stages of development.

Animals↗

Comparative susceptibility of Southeast Asian Anopheles mosquitoes to the simian malaria parasite Plasmodium cynomolgi.

Seven Anopheles species/isolates were compared with Anopheles dirus (control) for susceptibility to Plasmodium cynomolgi B strain. The mean numbers of oocysts in paired replicates of An. dirus and An. takasagoensis were not significantly different. The remaining test species had significantly fewer mean numbers of oocysts than Anopheles dirus (P less than 0.01). Anopheles dirus had the highest percentage of mosquitoes infected with P. cynomolgi sporozoites (82%). Of the test groups, Anopheles dirus B and An. takasagoensis had the highest percentage of mosquitoes with sporozoites, 77 and 78%, respectively. Fewer than 50% of Anopheles maculatus E and An. maculatus B (NN isolate) had sporozoites in the salivary glands. Anopheles maculatus B (HK isolate) and Anopheles philippinensis were the least susceptible, with fewer than 30% having sporozoites in the salivary glands.

Animals↗

Seasonal distribution and biting patterns of Anopheles mosquitoes in Costa Marques, Rondonia, Brazil.

Thirteen species of anopheline mosquitoes were collected in all-night human-bait indoor and outdoor collections at 5 houses from July 1986 through December 1987 in and near the town of Costa Marques, Rondonia, Brazil. Anopheles darlingi and An. deaneorum accounted for more than 92 and 6%, respectively, of all anophelines collected from human-bait outside houses and 90 and 9%, respectively, inside houses in the town. The diversity of anophelines was greater in human-bait collections in rural areas. However, An. darlingi still accounted for more than 90% of all the anophelines collected from human-bait inside and outside rural houses. Data on nocturnal and seasonal biting rhythms for the more common anophelines are given.

Animals↗

Tubal and peritoneal factors in the infertile woman: use of patient history in selection of diagnostic and therapeutic surgical procedures.

For facilities with both ambulatory and inpatient surgical capabilities, we have attempted to develop an efficient strategy for the evaluation of infertile women. The strategy was intended to (1) avoid inpatient laparoscopy, (2) minimize the number of patients having laparoscopy who subsequently required laparotomy, and (3) minimize hysterosalpingography (HSG). Patients were selected for ambulatory laparoscopy or inpatient laparotomy by means of an algorithm based on their history and the selective use of HSG. Laparoscopy was avoided in 18.1% of patients and HSG in 41.6% of patients. We conclude that, when both inpatient and outpatient surgical facilities are available, the evaluation of female infertility may not always require HSG or laparoscopy.

Algorithms↗

Colonization and maintenance of Anopheles deaneorum in Brazil.

Anopheles deaneorum, an important malaria vector and a member of the Anopheles albitarsis complex, was colonized by an artificial mating technique. Morphological and behavioral differences between An. deaneorum and An. albitarsis from Costa Marques, Rondonia, Brazil, are discussed. The essential methods and colonization techniques are described. Immature development and mortality rates were reduced when dried grass was added to larval rearing pans. Males frequently mate more than once using the force mating technique. However, insemination and larval eclosion rates decline as males are successively mated with unmated females.

Animals↗

The effects of lactation on bone mineral content in healthy postpartum women.

Bone mineral contents were estimated by dual photon absorptiometry of the lumbar spine (L2-L4) and single photon absorptiometry of the mid- and distal radius in 19 healthy women on their second postpartum day and at 6 months postpartum. All bone mineral measurements were performed by one technician, and the single and dual photon absorptiometry results were read by one observer. Daily oral calcium intakes were estimated from dietary histories obtained by a dietitian. Twelve women who breast-fed exclusively throughout the first 6 months postpartum were compared with seven formula-feeding women who did not breast-feed or who breast-fed for less than 3 months postpartum. No differences were found in age, parity, height, weight, or daily calcium intake between the breast- and formula-feeding women. Breast-feeding women had a significant decrease (averaging 6.5%) in bone mineral of the lumbar spine at 6 months postpartum as compared with 2 days postpartum (1.14 +/- 0.03 versus 1.22 +/- 0.03 g/cm2, mean +/- SEM; P less than .001), whereas no significant change occurred in the formula-feeding women at 6 months (1.24 +/- 0.03 versus 1.26 +/- 0.04 g/cm2). At 6 months postpartum, the breast-feeding women had a significantly lower mean bone mineral content of the lumbar spine than did formula-feeding women (P less than .05). No significant changes were noted in bone mineral content of the mid- or distal radius in either group of women during the period of evaluation. We conclude that during the first 6 months postpartum, breast-feeding is associated with bone mineral loss from the lumbar spine, but not from the mid- or distal radius.

Adult↗

The value of serum antimicrosomal antibody testing in screening for symptomatic postpartum thyroid dysfunction.

We investigated the value of a screening program for postpartum thyroiditis in a heterogeneous American population and used serum antithyroid antibodies to identify postpartum women at risk. Blood was drawn from 1034 consecutive women on their second postpartum day and tested for antimicrosomal and antithyroglobulin antibodies by hemagglutination. Seventy-two women (7.0%) were seropositive for antimicrosomal antibodies, but only seven (0.7%) had antithyroglobulin antibodies. There was a significant difference in the racial prevalence of antimicrosomal antibodies, with seropositivity in 52 of 588 white women (8.8%) versus nine of 367 black women (2.5%; p less than 0.001). Thirty-four of 51 (67%) antimicrosomal seropositive women followed at least 6 months post partum developed biochemical thyroid dysfunction and 20 of these patients required treatment for hypothyroidism. The mean (+/- SEM) serum thyroxine and thyrotropin levels in these patients before treatment were 3.0 +/- 0.3 micrograms/dl (normal 6.1 to 12.3 micrograms/dl) and 77 +/- 17 mU/L (normal 0.3 to 4.0 mU/L), respectively. Psychologic interviews revealed a significant increase in impaired concentration, carelessness, depression, and total complaints when patients with postpartum hypothyroidism were compared with postpartum euthyroid women. Medical evidence now suggests that postpartum thyroiditis is a common event and causes significant symptoms in women who develop hypothyroidism. Therefore, we propose that serum antimicrosomal antibody testing of postpartum women provides a feasible cost-effective screening method of identifying women likely to suffer from this disease.

Autoantibodies↗