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Biomedical subjects

L Cunningham

Publications and source records attributed to L Cunningham.

At least 37 records · Page 2Linked to original sources
PubMed1994

Bupropion in tricyclic antidepressant nonresponders with unipolar major depressive disorder.

Tricyclic antidepressant (TCA) medications are among the most widely used pharmacologic treatments for depression. However, a substantial number of patients fail to respond to these agents. Few standardized trials of pharmacologic treatments for TCA nonresponders are available. Bupropion has an apparently different mechanism of action than TCAs and represents a possible treatment for the TCA nonresponder. Based on positive results from pilot studies, a standardized study evaluating bupropion in TCA nonresponders was conducted. Forty-one depressed outpatients who had failed to respond to adequate documented TCA treatment, defined by specific criteria of dosage, duration, and plasma concentrations, entered a 1-week single-blind placebo phase, followed by an open 8-week bupropion treatment phase utilizing doses of up to the maximum daily dose of 450 mg. Response was measured by change on the Hamilton Depression Rating Scale (HAM-D), Clinical Global Impressions-Severity (CGI-S) and Improvement (CGI-I) Scales, and the Hamilton Anxiety Rating Scale (HAM-A). Bupropion treatment resulted in an improvement in depression on all outcome measures. Forty-nine percent were considered "responders," in that they achieved > or = 50% improvement on the 28-item HAM-D. Fifty-four percent were classified as responders based on a CGI-I rating of much or very much improved. Statistically significant improvement in depressive symptoms, measured by mean scores for the HAM-D, CGI-S, and HAM-A, was achieved at the end of the study (as compared to baseline). Twelve patients (32%) had a HAM-D score of < or = 10 at termination.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Single-channel to multichannel conversions in pediatric cochlear implant recipients.

Speech perception skills were measured in five children who had received a 3M/House single-channel cochlear implant and were subsequently upgraded to a multichannel cochlear implant (Nucleus). A rationale was developed based upon performance with the single-channel device and anticipated performance with the multichannel device. All subjects demonstrated improved acoustic thresholds with the multichannel device. Three of the children demonstrated improvements on identification tasks and two on word recognition tasks.

Adolescent↗
PubMed1993

Attenuation of a reactivated cardiovirulent coxsackievirus B3: The 5'-nontranslated region does not contain major attenuation determinants.

To investigate the molecular basis of pathogenicity of Coxsackieviruses, a virus was reactivated by transfection from a full-length cDNA clone derived from cardiovirulent Coxsackievirus B3 (CVB3). The reactivated virus, rCVB3, was passaged serially in human dermatofibroblasts (HDF). No cytopathic effect was observed up to 12 days after inoculation with rCVB3 or early-passage virus, although disintegration of the monolayers was observed with late-passage virus (10th to 14th passages). Approximately 10% of HDF inoculated with rCVB3 were positive for viral antigens by immunofluorescence using enterovirus- or CVB3-specific monoclonal antibodies. These observations, together with the low infectivity titre of rCVB3 in HDF, suggests that HDF initially support only carrier state infection. After the 14th passage, the cardiovirulence of passaged virus (p14V) in mice was attenuated by a factor of > 10(4). Phenotypic changes of plaque size were also noticed in p14V: An attenuated variant (p14V-1) that produced larger plaques than rCVB3 in Vero cells has been plaque purified. The 5'-terminus of the genome of attenuant p14V-1 was amplified by polymerase chain reaction (PCR) and its sequence determined. Only one point mutation was found within the 5'-nontranslated region (5'NTR) at position 690 (A to U) compared to the viral RNA sequence obtained for rCVB3. An intertypic chimeric virus was reactivated from a cDNA clone after replacing the 5'-terminal 891 nucleotides of the wild-type genome with the corresponding region of the attenuant p14V-1. This chimeric virus, CB3/p14V-1/1, produced wild-type plaques in Vero cells and showed cardiovirulence similar to that of rCVB3 in mice.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Chronic hyperplastic sinusitis: association of tissue eosinophilia with mRNA expression of granulocyte-macrophage colony-stimulating factor and interleukin-3.

BACKGROUND: We investigated the association among tissue eosinophilia, cellular infiltration, and cytokine mRNA expression in chronic hyperplastic sinusitis (CHS). METHODS: Percutaneous biopsies of the maxillary sinuses and nasal polyps were performed in 12 adult patients (six men and six women) of whom seven were nonallergic and 11 were asthmatic. Tissues were compared with biopsy specimens from the inferior and middle turbinates of normal control subjects. RESULTS: Histologically, an eosinophil-predominant inflammatory infiltrate was seen in 10 of 12 patients, whereas a mild to moderate neutrophilic infiltrate was seen in 4 of 12 patients. As determined by immunocytochemistry, diseased tissues and normal control tissues differed significantly in terms of the number of activated (EG2+) eosinophils (p = 0.005) but not in terms of CD3+ or CD4+ T lymphocytes, elastase-positive neutrophils or CD68+ macrophages. The number of eosinophils did not correlate with that of any other cell type. By in situ hybridization, CHS tissues showed significantly higher numbers of granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin (IL)-3 mRNA-positive cells than normal control tissues (p = 0.002 and 0.0005, respectively) per high-powered field. There was a significant correlation between the number of infiltrating EG2+ eosinophils and cells that expressed mRNA for GM-CSF (r = 0.60, p = 0.041) or IL-3 (r = 0.69, p = 0.013). Furthermore, epithelial cells did not show detectable mRNA expression for GM-CSF or IL-3. No significant correlation was found between IL-5 mRNA expression and infiltrating EG2+ eosinophils in diseased tissues. However, the IL-5 density was significantly higher in the five patients with CHS who had positive allergy skin test results than in the seven patients with negative skin test results (p = 0.017) or in normal control subjects. CONCLUSIONS: Our data support a role for GM-CSF and IL-3 in the eosinophilia characteristic of CHS and show that IL-5 mRNA expression is not a prominent feature of nonallergic inflammation. The cellular sources of GM-CSF and IL-3 in CHS remain to be definitely determined.

Adult↗
PubMed1993

Persistence of enterovirus RNA in muscle biopsy samples suggests that some cases of chronic fatigue syndrome result from a previous, inflammatory viral myopathy.

Molecular hybridization using an enterovirus group specific probe detected virus RNA in muscle biopsy samples from 25 of 96 cases of inflammatory muscle disease and similarly from 41 of 158 cases of postviral fatigue syndrome (PFS). Enterovirus RNA was detected in only two of 152 samples of control muscle. The inflammatory myopathy group comprised patients with polymyositis (PM), juvenile dermatomyositis (JDM) or adult dermatomyositis (DM), and all showed the presence of an inflammatory infiltrate and fiber necrosis on histological examination of a muscle biopsy sample. In contrast, muscle samples from the PFS group were histologically normal except for non-specific changes such as occasional single fiber atrophy. By analogy with enteroviral myocarditis, which can progress to a post-inflammatory disease with persistence of virus in myocardium and disposes to the rapid development of dilated cardiomyopathy, we propose that PFS syndrome may be a sequela of a previous inflammatory viral myopathy.

Biopsy↗
PubMed1991

Cytology of treated and minimal Pneumocystis carinii pneumonia and a pitfall of the Grocott methenamine silver stain.

To clarify the role of foamy alveolar casts (FACs) in the diagnosis of Pneumocystis carinii pneumonia (PCP), we retrospectively reviewed Papanicolaou (Pap)- and Grocott methenamine silver (GMS)-stained slides from 205 bronchial specimens submitted for suspected opportunistic lung infection. FACs containing sporozoites were seen in 86 cases, all with positive GMS. FACs were absent in 119 cases with negative GMS. In patients previously treated for PCP, Pap showed FAC-like material which lacked sporozoites. GMS demonstrated clumped degenerated Pneumocystis carinii (PC) cysts. In 17 GMS-positive cases there were no FACs on Pap due to sampling error and low burden of organisms. Morphologic features of macrophages in these cases can suggest the presence of PC. When FACs are lacking, a special stain is required. When GMS is used, the control must contain PC to avoid a false negative GMS. The inconsistent uptake of GMS by PC is a pitfall which is distinct from sampling error and which to our knowledge has not been previously reported.

Bronchi↗
PubMed1991

Molecular probes for detection of persisting enterovirus infection of human heart and their prognostic value.

Enteroviruses are well recognized in the aetiology of myocarditis. Molecular hybridization using enterovirus group-specific probes shows that virus can be detected in endomyocardial biopsies and persists in myocardium after the inflammation heals. Virus persistence is associated with the subsequent development of dilated cardiomyopathy, progressing to end-stage disease requiring cardiac transplantation. Infectious virus cannot usually be isolated from myocardium nor can virus-specific antigens be detected after the initial inflammatory stage. Patients with healed myocarditis or dilated cardiomyopathy may have no histological evidence of inflammation despite detection of virus-specific RNA sequences by molecular hybridization. Persisting enterovirus RNA in dilated cardiomyopathy is the strongest known predictor of poor prognosis. The molecular mechanism of virus persistence is the selection of defective virus mutants during the initial phase of disease.

Cardiomyopathy, Dilated↗
PubMed1991

Persistent virus infection of muscle in postviral fatigue syndrome.

Nucleic acid was extracted from muscle biopsy samples from a series of highly selected patients suffering from chronic muscle fatiguability following a viral infection (Postviral Fatigue Syndrome: PVFS). Samples were examined for the presence of enteroviral RNA sequences or Epstein-Barr (EBV) virus DNA sequences by molecular hybridisation as these two agents have been implicated by retrospective serology in the aetiology of PVFS. We found enteroviral RNA in 24% of biopsy samples and EBV DNA in a further 9% of biopsy samples: no biopsy was positive for both enteroviral RNA and EBV DNA. In addition, in the case of enteroviruses we found that the persisting virus is defective in control of RNA replication as both strands of enteroviral RNA are present in similar amounts: this is unlike the asymmetric synthesis of genomic RNA seen in a productive, cytolytic enterovirus infection. The implications of these data in relation to mechanisms of viral persistence and muscle dysfunction are discussed.

DNA, Viral↗
PubMed1990

Persistence of enteroviral RNA in chronic fatigue syndrome is associated with the abnormal production of equal amounts of positive and negative strands of enteroviral RNA.

A subgenomic restriction fragment from cDNA prepared from Coxsackie B2 virus (CVB2) RNA was subcloned into a riboprobe vector allowing the production of enteroviral group-specific RNA probes complementary to either the positive (genomic) or negative (template) strand of enteroviral RNA. These riboprobes were used to follow productive infection of cultured cells by CVB2; as expected, positive strand RNA was synthesized in approximately 100-fold excess over negative strand. RNA was extracted from muscle biopsy samples from patients with chronic fatigue syndrome and probed for the presence of enteroviral RNA. In cases where enteroviral RNA was detected the amounts of positive and negative strands of enteroviral RNA were approximately equal, in contrast to the situation in lytic infection of cultured cells. This suggests that enterovirus persistence in muscle is due to a defect in control of viral RNA synthesis.

Animals↗
PubMed1990

Spontaneous decay of oxidized ascorbic acid (dehydro-L-ascorbic acid) evaluated by high-pressure liquid chromatography.

We applied high-pressure liquid chromatography to assess the decomposition of the oxidized form of vitamin C, dehydro-L-ascorbic acid. We selected experimental conditions that might represent a wide variety of clinical and research procedures. Decay of dehydro-L-ascorbic acid proceeded much more rapidly at high pH (7-8) than at low pH (3-5) and was more rapid at 37 or 45 degrees C than at 0 or 23 degrees C. When evaluated at pH 6.6, the percent decay was somewhat more rapid from an initial concentration of 1000 mumol/L than at 5-10 mumol/L. The analytical procedure (HPLC) provided useful information about the rate of decay under various conditions. This may facilitate future biological and clinical studies that require a distinction between the oxidized and reduced forms of vitamin C.

Ascorbic Acid↗
PubMed1989

End-stage dilated cardiomyopathy. Persistence of enterovirus RNA in myocardium at cardiac transplantation and lack of immune response.

Tissue from the explanted hearts of 21 patients with idiopathic dilated cardiomyopathy or 19 patients with other specific heart muscle diseases were investigated for presence of enterovirus-specific RNA with an enterovirus group-specific cDNA probe. This was complementary to coxsackievirus B2 RNA sequences between nucleotide numbers 6,550 and 7,400, which are highly conserved between enteroviruses. Hearts from six patients with dilated cardiomyopathy and one patient with ischemic heart disease were found to contain virus RNA. Serology revealed that only one patient (dilated cardiomyopathy group) was positive for coxsackievirus B-specific IgM but negative for virus RNA in the myocardium. Quantitation of leukocytes and T-lymphocytes in the myocardium and expression of major histocompatibility locus antigens revealed no significant differences associated with persistence of virus RNA. These data demonstrate that enterovirus RNA persists in myocardium of a significant proportion of patients with end-stage dilated cardiomyopathy in the absence of a continuing cell-mediated or humoral immune response.

Adolescent↗
PubMed1989

Treatment of tracheobronchial granular cell myoblastomas with endoscopic bipolar cautery.

Granular cell myoblastomas of the trachea and right upper lobe bronchus were discovered incidentally during therapeutic bronchoscopy. Because of their propensity to cause airway compromise and distal atelectasis, ablation of both lesions was undertaken. This is the first reported case of bipolar cautery of GCM through a flexible fiberoptic bronchoscope. Small tumor size and lack of atelectasis permitted utilization of this technique. Long-term follow-up is necessary to compare this therapy with other nonresectional therapies.

Bronchial Neoplasms↗
PubMed1986

Immunoperoxidase staining of carcinoembryonic antigen as a prognostic indicator in colorectal carcinoma.

Immunoperoxidase staining for carcinoembryonic antigen (CEA) was performed on 192 colorectal carcinomas to determine: whether tissue staining can be substituted for preoperative serum CEA levels, and whether patient survival can be predicted by these parameters. The overall incidence of positive tissue staining was 75 percent, which was similar to the elevated serum level percentage of 73 percent. Both the serum CEA level and the CEA tissue stain correlated with patient survival in Dukes' stage C patients. There was no correlation between tissue CEA stain and tumor differentiation. Positive tissue stain and elevated preoperative serum CEA identified patients with poor prognosis in Dukes' stage D only. This study shows that tissue staining with immunoperoxidase may be substituted for preoperative serum levels for CEA. The combination of these two parameters, however, does not identify patients at greater risk for recurrence than either procedure alone.

Adenocarcinoma↗