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Biomedical subjects

D A Lewis

Publications and source records attributed to D A Lewis.

At least 181 records · Page 10Linked to original sources
PubMed1995

A one-year survey of Neisseria gonorrhoeae isolated from patients attending an east London genitourinary medicine clinic: antibiotic susceptibility patterns and patients' characteristics.

OBJECTIVES: To collect epidemiological data on gonococcal infection in an east London genitourinary medicine (GUM) clinic; to perform antibiotic susceptibility testing on Neisseria gonorrhoeae isolates and relate results to patient data; to assess the efficacy of current first-line antibiotic therapy for treating gonorrhoea. METHODS: Gonococcal isolates were collected from 113 patients attending the GUM clinic at Newham General Hospital over a one year period. Isolates (104) were tested for susceptibility to various antibiotics. Plasmid profiles were obtained for penicillinase producing gonococci (PPNG) and isolates exhibiting high-level tetracycline resistance (TRNG). Epidemiological information was collected from clinic attenders by routine note-taking. RESULTS: PPNG (16) accounted for 15% of isolates tested, only three being acquired outside the United Kingdom (U.K.). Plasmid typing showed three types of beta-lactamase-encoding plasmids were represented (2.9 MDa, 3.2 MDa and 4.4 MDa). Amongst the non-PPNG isolates, high-level chromosomal resistance to penicillin (CMRNG) was found in 3.5%, intermediate resistance in 57.5% and full susceptibility in 39%. One isolate showed decreased susceptibility to ciprofloxacin (MIC = 0.06 mg/l). Three PPNG isolates also possessed a 25.2 MDa plasmid and expressed high-level tetracycline resistance encoded by tetM. All isolates were susceptible to cefixime, cefotaxime, azithromycin and spectinomycin. Most gonorrhoea (90%) was seen in local residents. The male:female case ratio was 2:1 with homosexually-acquired gonorrhoea accounting for only 3.5% of the total. Most patients (96%) had acquired gonorrhoea in the U.K.. A past history of gonorrhoea was more frequent in male patients. Concurrent chlamydial infection was seen in 31% females and 16% males. CONCLUSIONS: The high PPNG rate supports a previous decision to change first-line therapy from amoxycillin with probenecid to ciprofloxacin. There was no evidence of clinical treatment failure with ciprofloxacin. Cefixime, cefotaxime, azithromycin and spectinomycin all appear to be suitable alternative therapies. Acquisition of gonorrhoea abroad was associated with isolates exhibiting penicillin resistance but such isolates were also obtained from patients infected locally and without a history of foreign travel.

Adult↗
PubMed1995

Predicting the "revolving door" phenomenon among patients with schizophrenic, schizoaffective, and affective disorders.

OBJECTIVE: A subpopulation of chronically mentally ill patients, sometimes referred to as "revolving door" patients, are frequently readmitted to psychiatric units. This study examined the relationships among demographic features, diagnostic characteristics, and frequency of hospitalization of patients from four state hospitals. METHOD: Two semistructured, standardized instruments, the Schedule for Affective Disorders and Schizophrenia and a life events history, were administered to 135 inpatients who met the Research Diagnostic Criteria for schizophrenia (N = 56), schizoaffective disorder (N = 33), unipolar major depressive disorder (N = 23), and bipolar disorder (N = 23). Criminal history was assessed by arrest records. The main outcome measure was the number of hospitalizations. RESULTS: Chi-square and trend test analyses indicated that substance abuse and noncompliance with medication regimens were significantly associated with higher frequencies of hospitalization. A multiple regression model, which included alcohol/drug problems, medication noncompliance, and six sociodemographic and diagnostic variables (age, gender, race, marital status, years of education, and diagnosis) accounted for a significant proportion of the ability to predict frequency of hospitalization. Half of this predictability was due to the relationship of substance abuse and medication noncompliance with number of hospitalizations. CONCLUSIONS: Alcohol/drug problems and noncompliance with medication were the most important factors related to frequency of hospitalization. Preventing these behaviors through patient education may reduce rehospitalization rates.

Adult↗
PubMed1995

State psychiatric hospital patients with past arrests for violent crimes.

OBJECTIVE: This study examined associations between four types of major psychopathology--schizophrenia, schizoaffective disorder, and bipolar and unipolar affective disorders--and history of violent crime. The effects of demographic variables, substance abuse, psychosis, and paranoia on history of violent crime were also determined. METHODS: Diagnostic assessments using the Schedule for Affective Disorders and Schizophrenia and Research Diagnostic Criteria identified 172 state hospital inpatients with the four diagnoses of interest, as well as those with co-existing substance use disorders. Based on arrest records, patients were categorized according to the most violent crime for which they had been arrested. RESULTS: Patients with schizoaffective disorder were significantly more likely than those in the other diagnostic groups to have been arrested for a violent crime. Similar results were found for psychotic patients compared with nonpsychotic patients, patients who had paranoid schizophrenia compared with patients who had schizophrenia without paranoid features, and patients who had co-existing substance abuse compared with those with no history of substance abuse. Patients from racial minority groups and male patients were also more likely than white patients and female patients to have been arrested for a violent crime. CONCLUSIONS: Demographic features, a diagnosis of schizoaffective disorder, psychosis, paranoid symptoms, and substance abuse may all be associated with violent behavior.

Adolescent↗
PubMed1994

Expression and distribution of two isoforms of tyrosine hydroxylase in macaque monkey brain.

In humans, the RNA for tyrosine hydroxylase (TH), the rate-limiting enzyme in the synthesis of catecholamines, can undergo alternative splicing to produce four different types of mRNA. Each of the predicted TH protein forms has been shown to be expressed in human brain, but constraints inherent in human postmortem studies require the use of an animal model to further explore the functional significance of multiple TH isoforms. Since the anatomical organization of catecholaminergic systems in Old World macaque monkeys appears to accurately predict their organization in humans, we used antibodies that selectively recognize each of the human TH isoforms to determine the expression and distribution of TH isoforms in monkey brain. Blot immunolabeling and immunocytochemical techniques demonstrated that catecholaminergic neurons of monkey brain express both type 1 and type 2 TH, but not type 3 or type 4. Thus, monkeys differ in the number of TH isoforms expressed in brain both from rodents (type 1 TH only) and humans (types 1-4 TH). In some catecholaminergic neurons and axon terminals of human brain, only type 1 TH immunoreactivity was detectable, suggesting that the selective expression of a single isoform could occur or that TH isoforms might differ in their accessibility to or engagement with cell trafficking mechanisms. However, in monkeys there was no evidence for the selective expression or distribution of either type 1 or type 2 TH in any of the catecholaminergic cell bodies or terminal fields examined. In addition, quantitative blot immunolabeling studies demonstrated that type 1 and type 2 TH were present in the same relative abundances in monkey substantia nigra and caudate nucleus. Furthermore, studies in monkeys designed to model the human postmortem state revealed that the apparently selective distribution of TH isoforms seen in the human study could be created by postmortem effects. In summary, in contrast to nonprimate species, multiple protein isoforms of TH are expressed in monkey brain as well as in human brain. Although the precise functional role of each isoform has not been determined, their presence suggests that the regulation of catecholamine biosynthesis may be more complex and subject to alternative modes of regulation in primates than in nonprimate species. In addition, the difference between monkeys and humans in the number of TH isoforms may provide insight into a molecular basis for species differences in cognitive and other brain functions. However, both type 1 and type 2 TH, the two predominant isoforms of human TH, are expressed in monkey brain.(ABSTRACT TRUNCATED AT 400 WORDS)

Amino Acid Sequence↗
PubMed1994

Local circuit neurons immunoreactive for calretinin, calbindin D-28k or parvalbumin in monkey prefrontal cortex: distribution and morphology.

In the cerebral cortex, local circuit neurons provide critical inhibitory control over the activity of pyramidal neurons, the major class of excitatory efferent cortical cells. The calcium-binding proteins, calretinin, calbindin, and parvalbumin, are expressed in a variety of cortical local circuit neurons. However, in the primate prefrontal cortex, relatively little is known, especially with regard to calretinin, about the specific classes or distribution of local circuit neurons that contain these calcium-binding proteins. In this study, we used immunohistochemical techniques to characterize and compare the morphological features and distribution in macaque monkey prefrontal cortex of local circuit neurons that contain each of these calcium-binding proteins. On the basis of the axonal features of the labeled neurons, and correlations with previous Golgi studies, calretinin appeared to be present in double-bouquet neurons, calbindin in neurogliaform neurons and Martinotti cells, and parvalbumin in chandelier and wide arbor (basket) neurons. Calretinin was also found in other cell populations, such as a distinctive group of large neurons in the infragranular layers, but it was not possible to assign these neurons to a known cell class. In addition, although the animals studied were adults, immunoreactivity for both calretinin and calbindin was found in Cajal-Retzius neurons of layer I. Dual labeling studies confirmed that with the exception of the Cajal-Retzius neurons, each calcium-binding protein was expressed in separate populations of prefrontal cortical neurons. Comparisons of the laminar distributions of the labeled neurons also indicated that these calcium-binding proteins were segregated into discrete neuronal populations. Calretinin-positive neurons were present in greatest density in deep layer I and layer II, calbindin-immunoreactive cells were most dense in layers II-superficial III, and parvalbumin-containing neurons were present in greatest density in the middle cortical layers. In addition, the relative density of calretinin-labeled neurons was approximately twice that of the calbindin- and parvalbumin-positive neurons. However, within each group of labeled neurons, their laminar distribution and relative density did not differ substantially across regions of the prefrontal cortex. These findings demonstrate that calretinin, calbindin, and parvalbumin are markers of separate populations of local circuit neurons in monkey prefrontal cortex, and that they may be useful tools in unraveling the intrinsic inhibitory circuitry of the primate prefrontal cortex in but normal and disease states.

Animals↗
PubMed1994

Characterization of humanized anti-TAC, an antibody directed against the interleukin 2 receptor, using electrospray ionization mass spectrometry by direct infusion, LC/MS, and MS/MS.

Characterization of a humanized monoclonal antibody (Hu-anti-TAC) directed against a surface protein expressed on T-lymphocytes was performed with an electrospray mass spectrometer. Capillary reversed-phase liquid chromatography (LC)/mass spectrometry (MS) and direct infusion MS were utilized along with tandem MS/MS analysis to confirm the sequence and to determine the sources of heterogeneity in Hu-anti-TAC. The MS analysis was performed on disulfide-reduced and trypsin-digested samples of the antibody. Two forms of diantennary carbohydrate structures were identified and found to be consistent with those reported for the human IgG1 framework. The analysis demonstrated that the N-terminus was modified by conversion of a glutamine residue to pyroglutamic acid. Another source of heterogeneity was the partial removal of the C-terminal lysine residue and was confirmed by mass calculations of tryptic peptides followed by MS/MS sequencing. This study demonstrates that the high sensitivity of electrospray mass spectrometry when combined with capillary chromatography can allow detailed characterization of microgram samples of high molecular weight proteins such as antibodies.

Amino Acid Sequence↗
PubMed1994

An outbreak of Campylobacter infection associated with the consumption of unpasteurised milk at a large festival in England.

Seventy-two laboratory confirmed cases of Campylobacter infection were identified in people who attended a large festival in England. A case-control study was undertaken to identify the vehicle of infection. Potential risk factors included the water supply to the site, and food, bottled spring water and unpasteurised milk sold at the event. Only the consumption of unpasteurised milk showed a statistical association with having a Campylobacter infection, strongly suggesting that this was the vehicle of infection.

Adolescent↗
PubMed1994

Prophylactic application of an intra-alveolar socket medicament to reduce postextraction complications in HIV-seropositive patients.

A prospective, controlled trial was performed to investigate the effect of a prophylactic socket medicament containing chlortetracycline, aspirin, and local anesthetics, in reducing the incidence of postextraction pain and infection in patients who are HIV-seropositive. Fifty patients were in the study; 25 received the experimental dressing and 25 had no dressing. Patients were asked to complete a questionnaire rating the pain at 24 hours and 48 hours after surgery. Seven days after extraction, socket healing was scored, and sockets with delayed healing sampled for culture. Four of 25 (16%) patients who received the experimental dressing and 8 of 25 (32%) controls experienced pain during the 48 hours after extraction (p = not significant). None of the group who received the experimental dressing and 7 of 25 (28%) in the control group had delayed healing, of these 4 had alveolar osteitis and three had infected sockets (p = 0.0096). We conclude that the experimental agent is useful as a prophylactic agent to reduce delayed healing in HIV-positive patients who undergo exodontia.

Acquired Immunodeficiency Syndrome↗
PubMed1994

The distribution of tyrosine hydroxylase-immunoreactive fibers in the human entorhinal cortex.

The entorhinal cortex plays an important role in learning and memory, and it has been implicated as a site of dysfunction in some neuropsychiatric disorders such as schizophrenia. The organization of many components of the neural circuitry of this region, including dopaminergic afferents, has not been studied in detail. Using immunohistochemical techniques, we examined the density and laminar distribution of axons immunoreactive for tyrosine hydroxylase, the rate limiting enzyme in catecholamine biosynthesis, in the entorhinal cortex of eight control human brains. The density of tyrosine hydroxylase-containing axons decreased from rostral to caudal regions of entorhinal cortex. In addition, there was a prominent medial to lateral gradient of increasing fiber density. This gradient extended into the adjacent transentorhinal cortex, which contained the highest density of labeled axons of the regions studied. The laminar distribution of tyrosine hydroxylase-containing fibers also differed among the subdivisions of the entorhinal cortex. A bilaminar pattern of labeled axons in layers deep I-superficial II and in deep layer VI was present in the intermediate and caudal subdivisions of entorhinal cortex. In contrast, the olfactory and rostral subdivisions, as well as portions of the transentorhinal region, contained a trilaminar pattern, with a high density of tyrosine hydroxylase-immunoreactive axons in layers deep I-superficial II, deep III-IV and deep VI. In addition, radially-oriented bands of labeled fibers were observed extending between deep layer I and layer III, particularly in the rostral subdivision of the entorhinal cortex. In summary, tyrosine hydroxylase-containing afferents to the human entorhinal cortex are distributed in a characteristic regional and laminar pattern, and the lateral regions of the entorhinal cortex and the adjacent transentorhinal cortex are particularly densely innervated. These data contribute to the understanding of the normal circuitry of the human entorhinal cortex, and are of potential relevance to the pathophysiology of certain neuropsychiatric disorders, such as schizophrenia.

Adult↗
PubMed1994

An in vitro study of proximal femoral allograft strains in revision hip arthroplasty.

Bone allografts are used frequently to replace bone stock subsequent to total hip arthroplasty. Revision of the failed hip replacement results in a complex structure of allograft bone, host bone and a metal femoral component. To evaluate the mechanics of the allograft-implant-host bone structure at the time of surgery, a strain gauge study was undertaken with six fresh/frozen human femora. Under defined loading conditions, cortical strain distributions were measured for five different cases: (1) normal bone, (2) bone with a femoral implant, (3) bone with the femoral component and an osteotomy at the mid-stem level of the implant (i.e. to stimulate the proximal allograft-host junction around the femoral stem), (4) bone with an osteotomy and an implant cemented into the 'allograft' (i.e. the proximal end of the femur), and (5) bone with an osteotomy and the implant cemented into both the proximal 'allograft' and the distal host bone. The results showed that, prior to making the osteotomy, proximal femoral strains were decreased with the insertion of a femoral stem. These strains were further decreased when an osteotomy had been made. This strain distribution did not change when the stem was cemented into the proximal 'allograft' bone, or cemented into the proximal 'allograft' and distal host bone. The decreases in strain for these test cases implied that the discontinuity between the bony segments caused an extended reduction in the tensile or compressive stresses transmitted through the cortices.(ABSTRACT TRUNCATED AT 250 WORDS)

Bone Transplantation↗
PubMed1994

Antibiotics at the extremes of age: choices and constraints.

Infection is a frequent cause of morbidity and mortality at the extremes of life. Its treatment is complicated by a lack of specificity in the clinical findings and wider range of pathogens than in other patients. For these reasons empirical therapy must cover a wide range of pathogens and yet, because the clinical findings may not even be due to infection, it should be as non-toxic as possible. It is also essential to investigate intensely before therapy so as to stand the best chance of making an aetiological diagnosis and possibly allowing a change to more directed therapy. Neonates in particular, but also the elderly, are susceptible to age-associated antibiotic toxicities, such as those from tetracyclines and chloramphenicol. Polypharmacy in the elderly renders them particularly liable to drug interactions. Both age groups have altered pharmacokinetics of antibiotics, including differences in absorption, distribution and elimination compared with healthy adults, and therapeutic drug monitoring may be needed more frequently as a result.

Aged↗
PubMed1994

Inaccuracy of noninvasive estimates of VD/VT in clinical exercise testing.

To evaluate the accuracy of noninvasive estimates of VD/VT in clinical exercise testing, we compared measurements of standard VD/VT with estimates based either on end-tidal CO2 (VD/VTET) or a published estimate of arterial PCO2 (VD/VTest) at peak exercise in 68 patients. Using regression analysis, we identified highly significant differences (p < 0.001) between each method and VD/VTstand across a broad range of observed VD/VT. Assuming a normal exercise VD/VT < or = 0.30, estimate methods were specific but were insensitive (50 percent for VD/VTET and 57 percent for VD/VTest) for identifying patients with abnormal gas exchange during exercise. Separate analysis of subgroups based on resting pulmonary function did not identify any group for which either method was acceptable. Our analysis showed that errors in estimating PaCO2, which are amplified by the Bohr equation when calculating VD/VT, are responsible for the inaccuracies of each noninvasive method. We conclude that noninvasive estimates of PaCO2 cannot replace measured arterial PCO2 for calculation of VD/VT during exercise.

Adult↗
PubMed1993

Topography of pyramidal neuron intrinsic connections in macaque monkey prefrontal cortex (areas 9 and 46).

An understanding of the normal organization of prefrontal cortex is essential to the recognition of pathology underlying human behavioral disorders believed to depend on this region. We have therefore studied the pattern of intrinsic intra- and interlaminar pyramidal neuron connectivity in prefrontal areas 9 and 46 (of Walker) in macaque monkey cerebral cortex (anterior to the arcuate sulcus between the principal sulcus and midline). We made focal (200-400 microns) injections of biocytin and mapped the pattern of orthogradely transported label. Injections made into the superficial layers label wide-ranging lateral projections within the same areas of prefrontal cortex. Projections local to such small injections form a narrow band of terminals in layers 1-3 (200-400 microns wide, 2-4 mm long) centered on the injection site. Collateral fibers spread orthogonal to this terminal band, making frequent bifurcations, to establish a series of parallel bands of terminals with uninnervated bands between, spaced regularly across the cortex (center to center 500-600 microns). The entire pattern of terminal label is stripe-like, with occasional narrower interbands and crosslinks between the bands, and can extend over 7-8 mm across the cortex. These projections arise from pyramidal neurons in layers 2, 3, and 5 and terminate in layers 1-3. The stripe-like pattern contrasts with patch-like patterns in other cortical regions (V1, V2, V4, motor, somatosensory) and is smaller in scale than stripe-like zones of corticocortical afferent terminals to this region, reported to be 300-750 microns wide and spaced 1.0-1.5 mm center to center.

Animals↗