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Biomedical subjects

L Jackson

Publications and source records attributed to L Jackson.

At least 73 records · Page 4Linked to original sources

Protecting the gut and the liver in the critically ill: effects of dopexamine.

OBJECTIVE: To measure the clinical effects of dopexamine on systemic and splanchnic perfusion in critically ill patients. DESIGN: Prospective study. SETTING: General intensive care unit. PATIENTS: Ten patients with sepsis syndrome, acute respiratory failure, and at least one other organ system in failure. The median age of the patients was 62.5 yrs (range 29 to 78), and the median admission Acute Physiology and Chronic Health Evaluation (APACHE) II score was 24 points (range 14 to 38). INTERVENTIONS: Timed infusion of dopexamine to a maximum dose of 6 micrograms/kg/min. MEASUREMENTS AND MAIN RESULTS: Systemic hemodynamics and oxygen transport variables were obtained from measurements after arterial and pulmonary artery catheterization. Gastric intramucosal pH and hepatic blood flow/function measurements were made by tonometry and indocyanine green clearance, respectively. All measurements were made before dopexamine infusion, after 1 hr of dopexamine infusion, and again 1 hr after the infusion ended. Cardiac index increased with dopexamine from a baseline median of 4.0 L/min/m2 (range 1.2 to 5.5) to 4.8 L/min/m2 (range 1.5 to 8.03) (p < .01), and returned to its previous level 1 hr after the infusion ended (median 4.0 L/min/m2 [range 1.4 to 5.8], p < .01). During dopexamine infusion, gastric intramucosal pH improved significantly from a median baseline level of 7.21 (range 7.04 to 7.50) to 7.28 (range 7.13 to 7.46, p < .05). This improvement in gastric intramucosal pH was maintained (median 7.36 [range 7.13 to 7.46]) after the infusion ended. Indocyanine green half-life decreased but not significantly with dopexamine (medians before and during the infusion were 6.6 and 6.3 mins, respectively). Indocyanine green half-life increased significantly 1 hr after the infusion ended (median 7.4 mins [range 4.4 to 14.8], p < .05), and changes in cardiac index correlated with changes in indocyanine green half-life (Rs2 = 0.60, p < .001). Changes in gastric intramucosal pH were unrelated to all other measurements. CONCLUSIONS: Dopexamine improves gastric intramucosal pH, and thus, splanchnic oxygenation. This improvement in gastric intramucosal pH appears to be independent of dopexamine's systemic effects.

Acute Disease↗

Terbutaline via pressurised metered dose inhaled (P-MDI) and Turbuhaler in highly reactive asthmatic patients.

There is some concern over the environmental consequences of chlorofluorocarbons (CFCs) used in pressurized metered-dose inhalers (p-MDIs). Turbuhaler was designed to deliver a drug as a dry powder without administering additives directly to the airways. The aim of this study was to evaluate the comparative irritant and bronchodilating effects of the same dose of terbutaline delivered by a p-MDI and via Turbuhaler. Ten symptomatic, asthmatic patients, with highly reactive airways (provocative concentration of methacholine producing a 20% fall in forced expiratory volume in one second (PC20) < 0.2 mg.ml-1), inhaled, on separate days, 0.25 mg terbutaline via p-MDI or Turbuhaler. Changes in airway calibre were followed as specific airways conductance (sGaw). On a third day, patients inhaled from a placebo p-MDI containing all constituents except terbutaline. The study was conducted in a single-blind fashion and in random order. There were no significant differences in baseline sGaw on any of the study days. Inhalation of terbutaline from the p-MDI produced a transient percentage fall in sGaw at 1 min, reaching a mean maximum +/- SD of 17 +/- 8% at 10 s and then returning to baseline value after 20 s, followed by a progressive increase in sGaw to a maximum of 39 +/- 45% above baseline at 45 min. In contrast, inhalation of terbutaline via Turbuhaler caused no significant bronchoconstriction (fall in sGaw, 3 +/- 16%) at 10 s and achieved a greater increase in sGaw, reaching 63 +/- 51% at 45 min, although just failing to reach statistical significance compared to terbutaline p-MDI inhalation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

de Lange syndrome: a clinical review of 310 individuals.

Three hundred ten individuals with a clinical diagnosis of de Lange syndrome were seen and examined in conjunction with the parent support group. One hundred thirty-four males and 176 females whose ages ranged from birth to 37 years made up the study group. Examination findings were recorded for those features described by de Lange in her original report of the syndrome to determine the frequency and significance of each. In addition, questionnaires were completed by 128 of these families and medical, growth and developmental records were collected. The clinical diagnosis seems best supported by the facial features of the syndrome including the long eyelashes and confluent eyebrows (synophrys), although additional characteristics are needed. Only 27% had the upper limb deficiencies commonly associated with the syndrome. Growth was retarded in nearly all individuals, often of prenatal onset. Medical problems occurred frequently and most often involved the eye and ear, as well as the cardiac and gastrointestinal systems. Of 14 deaths, almost half were secondary to cardiac or gastrointestinal complications. The recurrence risk in 377 sibs of the patients was calculated to be less than 1%. Although development lagged significantly in speech, most individuals developed good self-help skills. The study demonstrated a higher proportion of patients affected mildly with the syndrome than is commonly appreciated. This underscores the importance of early recognition and appropriate medical and developmental support.

Adolescent↗

Quantitative analysis of the metabolism of 9,10-dihydrobenzo[a]pyrene by induced rat liver microsomes.

The ability of reduced polycyclic aromatic hydrocarbons to be converted to their fully aromatic forms by the microsomal cytochrome P-450 mixed-function oxidases may assist in the explanation of the mutagenic and tumorigenic activities of these agents. The metabolic conversion of 9,10-dihydrobenzo[a]pyrene (9,10-DHB[a]P) to benzo[a]pyrene (B[a]P) and 9- and/or 10-hydroxy-9,10-DHB[a]P (OH-9,10-DHB[a]P) was quantitatively measured. In beta-naphthoflavone-induced rat liver microsomes, 9,10-DHB[a]P was metabolized to B[a]P with a specific activity of 1.51 nmol B[a]P formed/min/mg microsomal protein. The formation of B[a]P was directly related to incubation time and microsomal protein concentration. Similarly, 9,10-DHB[a]P was converted to OH-9,10-DHB[a]P with a specific activity of 4.48 nmol OH-9,10-DHB[a]P formed/min/mg microsomal protein. Its formation was directly related to incubation time and microsomal protein concentration. The possibility of OH-9,10-DHB[a]P as a metabolic intermediate to B[a]P is discussed.

Animals↗

Continuous chemotherapy in responsive metastatic breast cancer: a role for tumour markers?

A biochemical response index comprising ESR, CEA and CA 15.3 was evaluated in 67 patients with systemic breast cancer treated by chemotherapy; 55 were assessable by UICC criteria and the response index (96% of all UICC assessable patients). Marker changes at 2 and 4 months showed a highly significant correlation with the UICC assessed response at 3 and 6 months (P < 0.001); sensitivity 100%, specificity 87%; positive predictive value 85%; negative predictive value 100%. This index was then used to select out truly responsive patients and to prospectively direct their chemotherapy. Twenty-six responding (biochemical/clinical) patients were randomised to discontinue cytotoxics after 6 months and move to maintenance hormones (n = 13) or continue chemotherapy whilst the biochemical markers kept falling or remained within the normal range. Biochemical progression prompted a change of chemotherapy. Continuous chemotherapy in biochemically defined responders was associated with a significant lengthening of remission duration and an improved quality of life and survival. We are now using the index to routinely direct chemotherapy and select out true responders for maintenance chemotherapy.

Adult↗

Prenatal diagnosis in twin gestations: a comparison between second-trimester amniocentesis and first-trimester chorionic villus sampling.

OBJECTIVE: To evaluate prospectively the relative risks and accuracy of first-trimester chorionic villus sampling (CVS) and second-trimester amniocentesis in the genetic evaluation of twin gestations. METHODS: Between March 1984 and August 1990, patients presenting for prenatal diagnosis of a twin gestation of less than 12 weeks were offered sampling by either first-trimester CVS or amniocentesis at 16-18 weeks' gestation. Selection was based solely on patient preference and was obtained before ultrasound identification of placental position. Women presenting beyond 12 weeks' gestation were sampled by amniocentesis. Clinical and laboratory outcomes were evaluated. RESULTS: Eighty-one women had amniocentesis (nine of whom also had CVS), and 161 women had CVS. All fetuses in both groups were successfully sampled and karyotyped; 85.3% of the amniocentesis patients and 75.8% of the CVS patients were sampled in two or fewer passes (P = not significant). There were three cases of twin-twin villus contamination following CVS; one of these led to incorrect gender assignment because of erroneous laboratory interpretation. Loss of the entire pregnancy from the time of sampling until the 28th week of gestation followed amniocentesis in 2.9% of the cass and CVS in 3.2%. The total fetal loss rates were 9.3% for amniocentesis and 4.9% for CVS (P = not significant). When pregnancies having mosaic or abnormal karyotype results are excluded, the total amniocentesis loss rate remained 9.3% and the CVS loss rate became 3.9% (P < .05). CONCLUSION: In the hands of experienced operators, CVS is at least as safe and effective as amniocentesis for the prenatal diagnosis of twin gestations.

Abortion, Eugenic↗

Confirmation of a cryptic unbalanced translocation using whole chromosome fluorescence in situ hybridization.

We report on a 7-year-old boy with minor anomalies, growth retardation, and developmental delay with an initial 46,XY,der(18)t(18;?)(q23;?) chromosome constitution. To determine the origin of the additional chromosome segment, several candidate regions were identified including 4q and 18q. Clinical comparison showed more similarities to individuals with partial dup(4q) than to those with a dup(18q). Whole chromosome fluorescence in situ hybridization (FISH) was used to demonstrate the correct origin of the translocated region, clarifying the karyotype as 46,XY,der(18)t(4;18)(q28.2;q22.2), thus generating information of clinical importance. This illustrates the use of whole chromosome FISH to identify chromosome regions that cannot be determined conclusively using standard cytogenetic banding techniques.

Child↗

Ocular albinism in a male with del (6)(q13-q15): candidate region for autosomal recessive ocular albinism?

We describe a boy with an interstitial deletion of 6(q13-q15) and include "coarse" facial features, upslanting palpebral fissures, thin vermilion border of the upper lip, elongated philtrum, developmental delay, and profound hypotonia. The child's eye findings, pedigree, paucity of maternal ocular changes, and lack of melanin macroglobules in the skin suggest that this individual's phenotype is clinically similar to that of autosomal recessive ocular albinism. Though it is possible that this deletion and his ophthalmic disorder are coincidental, we postulate that the ocular albinism may be due to hemizygosity for a paternally derived ocular albinism gene located on chromosome 6 in the region q13-q15. This patient's deletion is secondary to a recombination of a maternal intrachromosomal inverted insertion of this region. Of the 7 reported 6q1 deletions, this is the only case that is due to a familial chromosome rearrangement.

Albinism, Ocular↗

Placental mosaicism in a case of 46,XY,-22,+t(22;22)(p11;q11) or i(22q) diagnosed at amniocentesis.

46,XY,-22,+t(22;22)(p11;q11) or i(22q) was diagnosed in 15/15 cells from two cultures from the amniotic fluid culture of a 31-year-old patient whose fetus demonstrated cystic hygroma on ultrasound. Cytogenetic studies performed on fetal skin from the abortus revealed the same karyotype as that seen on amniocentesis, but the placenta demonstrated a 46,XY/46,XY,-22,+t(22;22) or i(22q) mosaicism, with 65 per cent of the cells being 46,XY. This case provides an example of placental mosaicism for a normal male karyotype, while the fetus demonstrated non-mosaic trisomy 22.

Adult↗

Cytogenetic results from the U.S. Collaborative Study on CVS.

Cytogenetic data are presented for 11,473 chorionic villus sampling (CVS) procedures from nine centres in the U.S. NICHD collaborative study. A successful cytogenetic diagnosis was obtained in 99.7 per cent of cases, with data obtained from the direct method only (26 per cent), culture method only (42 per cent), or a combination of both (32 per cent). A total of 1.1 per cent of patients had a second CVS or amniocentesis procedure for reasons related to the cytogenetic diagnostic procedure, including laboratory failures (27 cases), maternal cell contamination (4 cases), or mosaic or ambiguous cytogenetic results (98 cases). There were no diagnostic errors involving trisomies for chromosomes 21, 18, and 13. For sex chromosome aneuploidies, one patient terminated her pregnancy on the basis of non-mosaic 47,XXX in the direct method prior to the availability of results from cultured cells. Subsequent analysis of the CVS cultures and fetal tissues showed only normal female cells. Other false-positive predictions involving non-mosaic aneuploidies (n = 13) were observed in the direct or culture method, but these cases involved rare aneuploidies: four cases of tetraploidy, two cases of trisomy 7, and one case each of trisomies 3, 8, 11, 15, 16, 20, and 22. This indicates that rare aneuploidies observed in the direct or culture method should be subjected to follow-up by amniocentesis. Two cases of unbalanced structural abnormalities detected in the direct method were not confirmed in cultured CVS or amniotic fluid. In addition, one structural rearrangement was misinterpreted as unbalanced from the direct method, leading to pregnancy termination prior to results from cultured cells showing a balanced, inherited translocation. False-negative results (n = 8) were observed only in the direct method, including one non-mosaic fetal abnormality (trisomy 18) detected by the culture method and seven cases of fetal mosaicism (all detected by the culture method). Mosaicism was observed in 0.8 per cent of all cases, while pseudomosaicism (including single trisomic cells) was observed in 1.6 per cent of cases. Mosaicism was observed with equal frequency in the direct and culture methods, but was confirmed as fetal mosaicism more often in cases from the culture method (24 per cent) than in cases from the direct method (10 per cent). The overall rate of maternal cell contamination was 1.8 per cent for the culture method, but there was only one case of incorrect sex prediction due to complete maternal cell contamination which resulted in the birth of a normal male.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

First-trimester biochemical and molecular diagnoses using chorionic villi: high accuracy in the U.S. collaborative study.

The accuracy of biochemical and molecular prenatal diagnoses using chorionic villi as the fetal source was assessed by seven centres participating in the NICHD collaborative study on the safety and accuracy of chorionic villus sampling (CVS) and amniocentesis. Of 601 pregnancies studied, biochemical methods were used to determine the diagnosis in 283 fetuses at risk for 35 different metabolic disorders. Fifteen different lysosomal storage diseases accounted for 81 per cent of the biochemical prenatal diagnoses performed, with 57 per cent of these pregnancies at risk for Tay-Sachs disease. No errors were made in the biochemical diagnoses that predicted affected or unaffected fetuses. However, the diagnoses of certain disorders (e.g., mucopolysacchariodosis type IH, metachromatic leukodystrophy, and Krabbe disease) occasionally required confirmatory studies in cultured amniocytes because the enzyme results were inconclusive in direct and/or cultured villi or due to the presence of a pseudodeficiency allele. Of these, only the diagnosis of a fetus at risk for Krabbe disease remained inconclusive after special studies to discriminate between mutant and pseudo-deficiency alleles. Recombinant DNA techniques were used to predict the diagnosis of 318 fetuses at risk for 16 different disorders in which the defective disease gene could be detected either directly or by linkage analysis to a nearby polymorphic marker. Of these, 32 per cent were for haemoglobinopathies, 25 per cent for cystic fibrosis, 24 per cent for Duchenne or Becker muscular dystrophy, and 7 per cent for haemophilias. Pregnancies at risk for known disorders with specific molecular lesions (e.g., sickle cell disease) were accurately diagnosed in direct and/or cultured villi. Diagnoses requiring analyses with closely linked polymorphic markers were occasionally uniformative or inconclusive. Maternal contamination was not reported in any biochemical or molecular-based diagnosis. These studies document the high accuracy and rapidity of both biochemical and mutation-specific prenatal diagnoses with direct and cultured chorionic villi.

Adult↗

Diagnosis and prenatal diagnosis of epidermolysis bullosa herpetiformis (Dowling-Meara) in a mother, two affected children, and an affected fetus.

In utero skin biopsy was performed on a fetus at risk of an uncertain form of epidermolysis bullosa (EB). The mother had produced two affected offspring diagnosed variously as having junctional or dystrophic EB. The two offspring and the fetus were products of different fathers. The mother claimed to have no disease and on clinical examination was without blisters. Examination of the fetal skin biopsy by light and electron microscopy revealed separation of the epidermal sheet from the majority of the biopsy sample, although occasional remnants of basal cells remained associated with the basement membrane. Aggregations of keratin filaments were observed within basal cells of the detached epidermis and in the attached basal cell remnants. The diagnosis was thus suggested to be epidermolysis bullosa Dowling-Meara. Re-review of the clinical and laboratory data from the affected infants revealed a clinical and histological pattern consistent with this diagnosis. Further discussion with the mother revealed that her skin had blistered as a child and that she presently had hyperkeratotic palms and soles. This history is consistent with the autosomal dominantly inherited epidermolysis bullosa herpetiformis (Dowling-Meara). This is the first reported prenatal diagnosis of EB Dowling-Meara. The morphological criteria of intraepidermal blistering and clumped keratin filaments within basal and immediately suprabasal cells characteristic of an affected individual postnatally also identified an affected fetus. There is, however, insufficient experience to be certain that these findings will hold from region to region in the body or among all affected fetuses, and thus prenatal diagnosis on a morphological basis should still be made with caution.

Adult↗

Varied potential risks of HIV infection among prostitutes.

To date, most HIV prevention programs targeting North American prostitutes have focused on individual behaviour change, and in particular, the consistent use of condoms between prostitutes and their clients. The organizational and societal level issues which may influence high risk practices within the working and private spheres have received relatively little attention. In addition, most prevention efforts have been limited to targeting the sub-population of street prostitutes. We outline here three different types of prostitutes (street prostitutes, escorts, and prostitutes who work part time in the service sector, i.e. barmaids and erotic massage therapists) known to work in many North American centres. In doing so, we suggest that potential risks of infection vary according to the type of prostitution, and that prevention programs must recognize the diversity in potential risk practices. Differences in the organization of work and working conditions of varied types of prostitutes may, in particular, influence risk practices while working. Some of the individual, organizational and societal level issues which influence risk practices among different types of prostitutes are presented. Much of the research involving HIV and prostitutes has accessed prostitutes at sites where street prostitutes are over-represented. Other studies are based on potentially baised samples as they have recruited prostitutes from medical clinics. Methodologic problems that influence attempts to obtain a representative sample of the prostitute population are discussed.

HIV Infections↗

Outbreaks of human enteric adenovirus types 40 and 41 in Houston day care centers.

OBJECTIVE: Human enteric adenovirus (EAd) types 40 and 41 cause diarrhea in young children, but little is known about their association with outbreaks of diarrhea in the child care setting. This study evaluated EAd as a cause of outbreaks of diarrhea among infants and toddlers in day care centers. DESIGN: Stool specimens were collected weekly regardless of symptoms during four periods from January 1986 to April 1991, from children 6 to 24 months of age enrolled in prospective studies of diarrhea in day care centers. All diarrhea stool specimens were tested for bacterial enteropathogens, rotavirus, and Giardia lamblia. A total of 131 outbreaks occurred during the study. No etiologic agent was identified in 77 outbreaks. Stool specimens from 75 of these 77 outbreaks and from another 21 outbreaks of diarrhea with a known cause were evaluated for EAd with a monoclonal antibody-based enzyme immunoassay. RESULTS: A total of 4402 stool specimens from 613 children from these 96 outbreaks was tested for EAd. The virus was detected in specimens collected during 10 outbreaks, 3 of which occurred in 1986, 3 in 1988, 1 in 1989, 1 in 1990, and 2 in 1991. Of 249 children, 94 (38%) in these 10 EAd outbreaks were infected with EAd. In 51 children (54%) the infection was symptomatic and in 43 (46%) it was asymptomatic. Outbreaks lasted 7 to 44 days (mean 24.5 days). Duration of EAd excretion ranged from 1 to 14 days (mean 3.9 days), with excretion occurring from 7 days (mean 2.6) before diarrhea began to 11 days (mean 5.3 days) after diarrhea stopped. CONCLUSION: Enteric adenovirus types 40 and 41 are an important cause of outbreaks of diarrhea among children attending day care centers, often involve children in more than one room, and frequently produce asymptomatic infection.

Adenovirus Infections, Human↗