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Biomedical subjects

P Lee

Publications and source records attributed to P Lee.

At least 163 records · Page 9Linked to original sources

Effects of neonatal ethanol exposure on cholinergic neurons of the rat medial septum.

The objective of this study was to determine the long-term effects of neonatal ethanol exposure on the cholinergic neurons in the medial septum (MS) of the rat. On postnatal day 4 (P4) pups were assigned to one of three groups: an ethanol-receiving, gastrostomized group (EtOH); a pair-fed, gastrostomized control group (GC); and a dam-reared suckle control group (SC). Gastrostomized pups were infused with ethanol-containing or control diet as a 9.1% v/v solution for two feedings on each day from P4 to P10. Choline acetyltransferase (ChAT) immunocytochemistry was analyzed at P60. Ethanol treatment resulted in long-lasting microencephaly in P60 EtOH animals. Ethanol exposure did not directly reduce ChAT-expressing (ChAT+) neuronal number, nor were changes noted in MS volume, mean area/section, or cell density as a result of ethanol treatment. Ethanol exposure reduced ChAT+ neuronal size in EtOH males compared with GC males but not SC males. No differences in ChAT+ neuronal size were noted in females. Thus, neonatal ethanol exposure, whereas producing long-lived microencephaly, has little effect on the cholinergic neurons of the adult rat MS.

Animals↗

Persistent air-leak in spontaneous pneumothorax--clinical course and outcome.

Persistent air-leak in patients with spontaneous pneumothorax (SP) is not uncommon and may present a management dilemma in those who are unfit or unwilling for surgery. Video-assisted thoracoscopic surgery (VATS) has been advocated in the management of patients with broncho-pleural fistulae (air-leak persisting beyond 7 days): however the optimum time for surgical intervention remains unclear. We reviewed the records of 130 episodes of SP in 115 patients over a 2-year period to determine clinical course and outcome, particularly with respect to duration of air-leak. There were 90 first episodes and 40 recurrent episodes. Eighty-one episodes (62%) occurred in patients with underlying lung disease (secondary pneumothorax). Initial management consisted of chest-tube drainage in 104 episodes (80%) occurring in 90 patients, percutaneous needle aspiration in five patients (4%) and observation in 21 episodes (16%) in 20 patients. In the group treated with chest-tube drainage, there was spontaneous resolution of air leak and lung re-expansion in 90 episodes (87%). The overall incidence of broncho-pleural fistula was 34.6%. In the primary SP group. 75% of air-leaks ceased by 7 days and 100% by 15 days. In the secondary SP group, 61% of air-leaks resolved by 7 days and 79% by 14 days, after which time resolution of air-leak proceeded at a much slower rate. Five patients underwent surgery while nine patients were discharged with residual pneumothoraces. There were no major complications or mortality. Based on our findings, we advocate surgery for patients with air-leak persisting beyond 14 days, while favouring a conservative approach before this time, as the majority of air-leaks (especially in patients with primary pneumothorax) would resolve by 14 days.

Adult↗

Transient increase in the alpha3-isoform of Na,K-ATPase in rat erythroblastic cells.

Using immunoelectron microscopy and isoform-specific antibodies against Na,K-ATPase to study changes in Na,K-ATPase in rat erythroblastic cells during maturation, we unexpectedly observed numerous antigenic sites against the alpha3-isoform in the cytoplasmic phase. There was an increase in the number of alpha3-isoforms after denucleation of the erythroblast. The increase was transient. As the reticulocyte matured into a red blood cell, the number of alpha3-isoforms was reduced drastically. This alpha3-isoform was distributed in a reticular pattern resembling the double layers of endoplasmic reticulum. Western blot analysis confirms the presence of the alpha3-isoform in these cells. X-ray microanalysis of the erythroid series of cells in the bone marrow shows that sodium concentration in the young reticulocyte is higher than that in the nucleated erythroblast. The reason for the transient increase in this pump protein is not clear. It is possible that the increase in sodium concentration in the reticulocyte plays a role in the increase in pump protein synthesis.

Animals↗

Large CAG/CTG repeats are associated with childhood-onset schizophrenia.

Recent studies have shown an association between trinucleotide repeat expansions (TREs) and adult-onset schizophrenia (AOS). Childhood-onset schizophrenia (COS) is a severe variant of schizophrenia with onset of symptoms before age 12 years. We have used the repeat expansion detection (RED) method to investigate the occurrence of repeat expansions in a group of well-characterized COS patients as well as a set of clinically related childhood-onset psychosis cases labeled 'multidimensionally impaired' (MDI). The difference observed in the CAG/CTG RED product distribution between normal (n = 44) and COS (n = 36) samples was only marginally significant (P = 0.036). However, male COS samples (n = 20) had a significantly different RED product distribution compared to male controls (n = 25, P = 0.002) with longer RED products in COS. No such difference was seen in females (ncont = 19; ncos = 16; P = 0.236). The difference remained significant between male COS (n = 12) and male controls (n = 24) when only Caucasian samples were used (P = 0.003). Similarly, the RED product distribution in male MDI samples (n = 18) was significantly different compared to male controls (P = 0.018). Some of the detected TREs in all three populations (COS, MDI and control) correlated with expanded alleles found at the CTG18.1 locus on chromosome 18. In conclusion, we have found an association between TREs and COS. This association is specifically significant in the male population. Thus, the occurrence of an expanded trinucleotide repeat may contribute to the genetic risk of COS, possibly in combination with other factors.

Adolescent↗

Lack of an association between a dopamine-4 receptor polymorphism and attention-deficit/hyperactivity disorder: genetic and brain morphometric analyses.

Although the etiology of attention-deficit/hyperactivity disorder (ADHD) is likely multifactorial, family, adoption, and twin studies suggest that genetic factors contribute significantly. Polymorphisms of the dopamine 4 receptor (DRD4) affect receptor binding, and one allele with seven tandem repeats in exon 3 (DRD4*7R) has been associated with ADHD. We examined this putative association in 41 children with severe ADHD and 56 healthy controls who were group matched for ethnicity and sex. The frequency of the DRD4*7R allele did not vary by diagnosis (0.220 vs 0.205 in patients and controls, respectively). Behavioral and brain anatomic MRI measures, previously found to discriminate patients from controls, did not differ significantly between subjects having and those lacking a DRD4*7R allele. These data do not support the reported association between DRD4*7R and the behavioral or brain morphometric phenotype associated with ADHD.

Alleles↗

The incidence and significance of fevers during treatment with antithymocyte globulin for aplastic anaemia.

Antithymocyte globulin (ATG) is a foreign protein used widely to treat aplastic anaemia (AA). Febrile reactions occurring during its administration may be impossible to distinguish clinically from fever due to sepsis, and are therefore routinely treated with intravenous antibiotics after collection of blood cultures. A statistically highly significant difference was found in positive blood cultures between 39 AA patients who developed fever during ATG therapy, and 38 febrile neutropenic patients with acute leukaemia. suggesting that most fevers developing during ATG treatment are not due to infection. It may therefore be reasonable to consider early discontinuation of intravenous antibiotics in patients who are clinically stable and have no proven sepsis.

Adolescent↗

Presence of immunoreactive alpha 3 subunit isoform of Na,K-ATPase in mitochondria of kidney.

BACKGROUND: Sodium-potassium-adenosinetriphosphatase (Na,K-ATPase) is the primary membrane enzyme responsible for the reabsorption of sodium ions in the kidney. It is known that in the nephron the major subunit isoforms of Na,K-ATPase are alpha 1 and beta 1. Previous reports on the presence of alpha 2 and alpha 3 isoforms in the kidney were mixed and controversial. METHODS: Techniques of ultrathin cryosectioning and immunoelectron microscopy were used to study the distribution of alpha subunit isoforms (alpha 1, alpha 2, alpha 3) and beta subunit (beta 1 isoform) of Na,K-ATPase in renal tubular cells. Western blot analysis was used to show the presence of the alpha 3 isoform in the extract of kidney mitochondria. RESULTS: We were able to confirm the previous finding that the alpha 1 isoform and the beta 1 isoform were the preponderant isoforms of the alpha and beta subunits of Na,K-ATPase in the basolateral membrane. In addition, we unexpectedly found the presence of the alpha 3 isoform in the mitochondria of rat renal tubular cells. The alpha 2 and alpha 3 isoforms were not observed in either the apical or basolateral membrane. CONCLUSIONS: Both immunoelectron microscopy and Western blot analysis of the rat kidney mitochondria confirm the presence of the alpha 3 isoform of Na,K-ATPase in the rat kidney mitochondria. The function of this enzyme in the mitochondria is not clear at this time.

Adenosine Triphosphate↗

Evidence of latent varicella-zoster virus in rat dorsal root ganglia.

Latent varicella-zoster virus (VZV) was studied in ganglia of rats that had been inoculated subcutaneously with either a high-passaged wild-type, a low-passaged wild-type, or the vaccine strain of virus using in situ hybridization. Nine of 11 rats injected with virus and no control rats developed serum VZV antibodies as demonstrated by fluorescent antibody membrane antigen. Polymerase chain reaction 2 weeks following inoculation did not detect viremia in the rats. VZV was detected by in situ hybridization in ganglia of 10 of the 11 infected rats but not in ganglia of the control rats. The distribution of VZV DNA is identical to that seen in humans; satellite cells and neurons contain VZV DNA. Although all animals received unilateral injections of virus, VZV DNA was in ipsilateral and contralateral ganglia in 6 animals, suggesting that virus replication and viremia had occurred.

Animals↗

Clinical nutrition: opportunity in a changing health care environment.

This article summarizes presentations from a satellite symposium, "Clinical Nutrition: Opportunity in a Changing Health Care Environment," held July 26, 1997, at the 37th annual meeting of the American Society for Clinical Nutrition in Montreal. The symposium was cosponsored by the American Society for Clinical Nutrition and the American Society for Parenteral and Enteral Nutrition. The diverse topics served as a practical forum for sharing information on innovative responses, concerns, and impediments in the rapidly evolving practice environment.

Enteral Nutrition↗

Case series: spectrum of neuroleptic-induced movement disorders and extrapyramidal side effects in childhood-onset schizophrenia.

OBJECTIVE: Neuroleptic-treated pediatric patients with childhood-onset schizophrenia (COS) are at risk for developing extrapyramidal side effects and involuntary movement disorders. A preliminary examination of the incidence of withdrawal dyskinesias (WD), tardive dyskinesia (TD), and extrapyramidal side effects in these patients is presented. METHOD: Thirty-four COS patients (mean age +/- SD, 14.2 +/- 2.1 years) were examined for TD using the Abnormal Involuntary Movements Scale and for extrapyramidal side effects using the Simpson-Angus Neurologic Rating Scale, after a 14- to 28-day drug-free period (n = 33), at week 6 of treatment and 2 to 4 years after completion of the study (n = 14). The mean (+/-SD) number of months of prior neuroleptic exposure for the group was 22.4 (15.0) months. RESULTS: Seventeen (50%) of 34 patients were noted to have either WD or TD at some point during their participation in the studies. The majority of patients experienced WD that were mainly in the orofacial region, transient in nature, and diminished with haloperidol and clozapine. Patients with TD/WD had greater levels of premorbid impairment (p = .02), increased severity of positive symptoms of schizophrenia (p < .01), and a trend toward more months of neuroleptic exposure (p = .10, one-tailed). CONCLUSIONS: A high proportion of COS patients were found to have TD/WD. The majority of these abnormal movements were not severe and generally improved over time. TD/WD in COS appears to be associated with greater premorbid impairment, severity of illness, and duration of neuroleptic exposure. J. Am. Acad.

Adolescent↗

Childhood-onset schizophrenia: an open-label study of olanzapine in adolescents.

OBJECTIVE: Olanzapine, a potent 5-HT2a/2c, dopamine D1D2D4 antagonist with anticholinergic activity, has a profile of known receptor affinity similar to that of clozapine. This pilot study examined the efficacy of olanzapine for treatment-refractory childhood-onset schizophrenia in eight patients who had received 8-week open-label trials. For comparison, data are included from 15 patients who had received 6-week open-label clozapine trials using identical rating instruments (largely by the same raters) in the same treatment setting. METHOD: Twenty-three children and adolescents with an onset of DSM-III-R schizophrenia by age 12 for whom at least two different typical neuroleptics had been ineffective participated in the two separate studies. Some of the patients were intolerant of clozapine, although it had been effective (n = 4). Patients receiving olanzapine were evaluated over 8 weeks with the Brief Psychiatric Rating Scale (BPRS), the Scale for the Assessment of Positive Symptoms, the Scale for the Assessment of Negative Symptoms, and the Clinical Global Impressions Scale for Improvement. RESULTS: For the eight patients who received olanzapine trials, at week 8 there was a 17% improvement in the BPRS total score, a 27% improvement in the Scale for the Assessment of Negative Symptoms, and a 1% improvement in the Scale for the Assessment of Positive Symptoms, relative to "ideal" admission status on typical neuroleptics. In contrast, the magnitude of the effect sizes for each of the clinical ratings was larger at week 6 of the previous clozapine trial than for an 8-week olanzapine trial, relative to admission status on typical neuroleptics. For the four children who had received both clozapine and olanzapine, BPRS total scores were significantly lower at week 6 of clozapine treatment compared with week 6 of olanzapine treatment (p = .03). CONCLUSION: These data provide preliminary evidence for the efficacy of olanzapine for some children and adolescents with treatment-refractory schizophrenia, but they also suggest the need for a more rigorous double-blind comparison of these two atypical antipsychotics.

Adolescent↗

Conformance with the preferred practice pattern for diabetic eye care.

OBJECTIVE: To investigate conformance with a practice guideline in the eye care of patients with diabetes. METHODS: The care of 210 patients with diabetes seen in a multispecialty eye care setting was compared with the recommendations of the American Academy of Ophthalmology's Preferred Practice Pattern. Criteria measured included appropriate classification of stage of disease, follow-up intervals based on stage of disease, and initiation of appropriate laser treatment. RESULTS: The 210 patients whose charts were reviewed showed high levels of conformance with recommended care patterns. All patients were appropriately classified. From 91-100% of patients were seen within the recommended time intervals and received laser treatment when indicated. CONCLUSION: The American Academy of Ophthalmology's Preferred Practice Pattern can be easily operationalized into review criteria. Application of these review criteria to one multispecialty eye care setting shows evidence of high rates of conformance with recommended care.

Diabetic Retinopathy↗

Effects of thrombin and protease nexin-1 on peripheral nerve regeneration.

Thrombin and serine protease inhibitors such as protease nexin-1 (PN-1) have been implicated in neurite outgrowth activity. We compared rat sciatic nerve regeneration in 10-mm silicone tubes, bridging an 8-mm nerve gap, that were prefilled with thrombin (1.5 IU) and PN-1 (50 micrograms/mL or 1 mg/mL) to those filled with saline solution (control). Neural regeneration and fibrinoid matrix progression (deposition of extracellular matrix) were analyzed at 1, 4, 17, and 21 days after silicone tube implantation. At 1 and 4 days after implantation, thrombin reduced fibrinoid matrix length propagation from both the proximal and distal transected nerve stumps, but PN-1 and saline did not interfere with matrix progression (p < .05). Seventeen days after implantation, the number of silicone tubes containing myelinated neuronal regenerates at the mid-tube region was 1 of 6 for thrombin, 6 of 9 for PN-1, and 6 of 10 for saline solution. Twenty-one days after implantation, 11 of 11 tubes with saline solution, 9 of 11 with PN-1 at 1 mg/mL, and 7 of 9 with PN-1 at 50 micrograms/mL had myelinated neural regenerates in the mid-silicone tube region, while only 2 of 9 thrombin-containing silicone tubes contained myelinated axons. There was no statistically significant difference in myelinated neurite regenerates at 17 and 21 days after implantation among silicone tubes prefilled with saline solution and PN-1 (50 micrograms/mL or 1 mg/mL). Thrombin interfered with matrix progression and significantly reduced the number of myelinated neurite regenerates (p = .01). The PN-1 and saline solutions did not inhibit matrix progression or affect the number of myelinated axonal regenerates (p = .92).

Amyloid beta-Protein Precursor↗

Axonal regeneration in severed peripheral facial nerve of the rabbit: relation of the number of axonal regenerates to behavioral and evoked muscle activity.

The minimum number of regenerating facial nerve myelinated motor axons that are required to innervate and activate the mimetic musculature is not known. We compare rabbit facial nerve regeneration following complete transectional injuries of the buccal division to the evoked and behavioral muscle activities of the quadratus labii superioris muscle of the rabbit in three experimental models: end-to-end direct anastomosis (N = 4), 8-mm autologous nerve grafts (N = 8), and 10-mm silicone chamber implants (N = 40). Data are presented as total numbers of regenerating myelinated axons that traverse the surgical repair and innervate the fascicles of the transected distal nerve stump, as well as the percentage of regenerating neurites, as compared to the preoperative normal controls. Five weeks after neural repair, direct end-to-end anastomosis regained more myelinated axons across the reconstructed defect (2,632 +/- 1,232; 67%) than silicone tube implants (2,006 +/- 445; 51%) or autologous cable graft repairs (1,660 +/- 1,169; 42%). However, only a small percentage of myelinated fibers innervated the intrafascicular region of the distal transected neural stump in direct anastomosis (948 +/- 168; 24%), silicone tube implants (670 +/- 275; 17%), or autologous nerve grafts (445 +/- 120; 12%) in rabbits that regained evoked and behavioral mimetic muscle activity. All rabbits with direct anastomosis and neural cable grafts regained motor activity, despite the fact that 66% of regenerating motor neurites in cable graft repairs and 54% in direct anastomosis were collateral sprouts that did not contribute to effective muscle activity. In 17 rabbits with neural regenerates within the silicone tube implants that did not regain mimetic activity, the mean number of regenerating myelinated motor axons across the defect was 504 +/- 419 (13%), and the mean number of axons that innervated the distal transected nerve stump fascicles was 277 +/- 128 (7%). Therefore, the minimal number of motor axons that is required to activate the quadratus labii superioris muscle is 12% of the original motor axon population of the normal buccal nerve division.

Anastomosis, Surgical↗

Childhood accidents: how a health promotion model may help.

The Health of the Nation targets have raised the profile of the need for accident prevention strategies for school children. Tannahill's health promotion model identifies a model of health, which in turn leads to a goal for health promotion. To develop effective health promotion and accident prevention nurses need to work in co-operation with other agencies. Health promotion in schools reaches a large audience and is an important means of reaching this age group. For accident prevention to be effective, hazards and/or risk taking behaviour should be reduced.

Accident Prevention↗

Well-being and treatment satisfaction in older people with diabetes.

OBJECTIVE: To measure well-being and treatment satisfaction and their correlates in older people with diabetes. RESEARCH DESIGN AND METHODS: A postal survey was conducted of 1,000 diabetic patients aged > or = 60 years, representing 56% of the resident older diabetic population in an inner-city health district with a largely indigenous population of 230,000 people and a widely varied socioeconomic mix. Well-being and treatment satisfaction were measured with diabetes-specific instruments and correlated with patient data held in a central register. RESULTS: There was an 81% response. The general well-being scores (median [interquartile range]) for patients on diet alone, tablets, and insulin were 54 (44-60), 53 (42-61), and 48 (35-56) (P < 0.001 comparing insulin with diet and tablets) compared with a scale maximum of 66. Treatment satisfaction scores were 35 (31-36), 35 (32-36), and 34 (30-36) (P < 0.001 comparing insulin with diet and tablets), scale maximum 36. Mean HbA1c concentrations were 5.0 +/- 1.4% (for patients on diet alone), 5.8 +/- 1.6% (tablets), and 6.6 +/- 1.7% (insulin) (P < 0.001 for each difference). Neither well-being nor treatment satisfaction correlated with HbA1c. Insulin-treated patients were younger and had been diabetic longer than non-insulin-treated patients; their well-being remained slightly, but significantly, lower when adjusted for age, sex, BMI, and diabetes duration, but treatment satisfaction was no longer significantly different. Women had lower well-being than men. CONCLUSIONS: It has proved possible to measure well-being and treatment satisfaction in a large community-based samples of older people with diabetes. At the level of glycemic control in this population, neither parameter correlated with HbA1c. The lower well-being in insulin-treated patients remained significant in multivariate analysis.

Aged↗