False polymerase chain reaction-based diagnosis: is it avoidable?
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False Negative Reactions↗
Biomedical subjects
J Berger
Publications and source records attributed to J Berger.
cDNA cloning and mRNA expression of the human adrenoleukodystrophy related protein (ALDRP), a peroxisomal ABC transporter.
We have cloned the cDNA containing the complete coding region of the human adrenoleukodystrophy related (ALDR) gene. The 2220-bp open reading frame encodes a 740-amino-acid polypeptide with a predicted molecular weight of 83.3 kDa. The human ALDR protein displays high similarity (62.8% identical amino acid residues) to the human adrenoleukodystrophy (ALD) gene. Analysis of ALDR expression revealed the presence of ALDR mRNA in a variety of human tissues, predominantly in brain and heart. This expression pattern is different from all other known peroxisomal ABC-transporters. Defects in the ALD gene are the primary cause of adrenoleukodystrophy, a demyelinating disorder of the central nervous system. The ALD protein (ALDP) and the ALDR gene product are peroxisomal membrane proteins belonging to the superfamily of transporters containing an ATP-binding cassette (ABC-transporters). All known peroxisomal ABC-transporters represent only one-half of a functional transporter. They are expected to form dimers either as a homodimer or as a heterodimer. ALDRP is a potential dimerization partner of ALDP or other peroxisomal ABC-transporters. The ALDR gene is a candidate for a modifier gene, accounting for the strikingly varying clinical courses of ALD observed even within a family.
ATP Binding Cassette Transporter, Subfamily D↗
Loss of retinoic acid receptor beta expression in breast cancer and morphologically normal adjacent tissue but not in the normal breast tissue distant from the cancer.
Retinoids and their receptors [retinoic acid receptors (RARs) and retinoid X receptors] play an important role in maintaining the balance between proliferation and apoptosis. Recently, Deng et al. [Science (Washington DC), 274: 2057-2059, 1996] reported a loss of heterozygosity on chromosome 3p24 in breast cancer specimens and the morphologically normal appearing adjacent tissue. The 3p24 locus includes, among other genes, the region coding for RAR-beta. This study was designed to determine whether there are abnormalities in the expression of retinoid receptors in surgical specimens of patients with breast cancer. In 14 patients, transcripts of nuclear retinoid receptors were detected by in situ hybridization in formalin-fixed, paraffin-embedded specimens by means of digoxigenin-labeled riboprobes specific for RAR-alpha, -beta and -gamma. We found RAR-alpha expressed in all specimens, whereas RAR-gamma was expressed in 100% of normal breast tissue but in only 11 of 14 tumorous lesions. RAR-beta was found in all cases of normal breast tissue localized distant from the tumor, but in 13 of 14 cases it was completely absent in the tumor and the morphologically normal appearing tissue adjacent to the tumor. One possibility to explain the suppression of RAR-beta is a mutation in the promoter region. Sequencing the DNA extracted from paraffin-embedded tumor tissue of the corresponding breast cancer specimens, we were not able to detect any mutation in the retinoic acid-responsive element. Our results clearly indicate a crucial role of RAR-beta in the carcinogenesis of breast cancer.
Breast↗
Occurrence, distribution, and phenotype of arylsulfatase A mutations in patients with metachromatic leukodystrophy.
Occurrence, distribution, and phenotype of arylsulfatase A (ASA) mutations were investigated in 27 patients with metachromatic leukodystrophy (MLD) from Central Europe, mainly from Austria (n = 15) and Poland (n = 9). Genomic DNA from leukocytes, fibroblasts, or paraffin-embedded, formalin-fixed brain or nerve tissue, respectively, was tested by natural or mutated primer-modulated PCR restriction, fragment length polymorphism for the eight most common European mutations: R84Q, S96F, 459+1G > A, I179S, A212V, 1204+1G > A, P426L, and 1401del11bp. The overall identification rate of unrelated MLD alleles was the highest, in adult (90%), medium in juvenile (50%), and lowest in late infantile (36%) MLD patients. The two common alleles, 459+1G > A and P426L, together accounted for 42% of all 50 unrelated MLD alleles investigated; I179S was observed in 6 of 50 MLD alleles (12%). Thus, I179S was far more frequent than hitherto thought and appears to be a third common mutation in Europe. Moreover, a different allelic distribution between Austrian and Polish juvenile patients was disclosed, indicating genetic heterogeneity of MLD even within Central Europe. The genotype-phenotype correlation suggested by Polten et al. [N Engl J Med 324:18-22, 1991] was not followed by all of our MLD patients. Moreover, some MLD patients with identical ASA mutations presented with different phenotypes. This may be due, at least in some cases, to the presence of an additional mutation on individual mutant alleles. Therefore, prediction of the clinical course from single mutation analysis is not possible.
Adult↗
All-solid-state miniaturized fluorescence sensor array for the determination of critical gases and electrolytes in blood.
We describe a six-channel, all-solid-state, miniaturized fluorescence sensor array for the precise determination of blood analytes for medical diagnostic purposes. The device features superblue LEDs as light sources, GRIN optics, and photodiodes, assembled according to pigtailing procedures (Bruno, A. E.; et al. Trends Anal. Chem. 1994, 13, 190-198). The numerical aperture of the fluorescence optics is 0.46, rendering a collection efficiency of 2.4%. The performance of this instrument has been evaluated in terms of dynamic response, linearity, channel reproducibility, reversibility, long-term drifts, photobleaching of indicator, cross-talk, ionic strength, and selectivity in pH measurements. The responses of the pH sensing membranes were optimized in the physiological range. Responses are linear with typical values of approximately 1.5 V/pH units, with limits of decision of 24 mV, which corresponds to pH resolutions of 0.03 pH unit. Under continuous illumination, using calibration buffers, the sensors display nonstatistical differences within 2 standard deviations over a period of 6 h, and it is shown that, under discontinuous illumination, the membranes can be used in more than 2000 measurements without need of calibration, in contrast to electrochemical sensors which require periodic calibration. After selecting the appropriate combination of LEDs, excitation and emission filters, and sensing membranes, the instrument was used to determine the concentrations of various critical blood analytes in buffer solutions in the various channels. Similar measurements in untreated blood reproduce the reported results.
Biosensing Techniques↗
Analysis of myopathy in a placebo-controlled zidovudine trial.
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Acquired Immunodeficiency Syndrome↗
Cholinesterases precede "ON-OFF" channel dichotomy in the embryonic chick retina before onset of synaptogenesis.
Retinal physiology is balanced by the interplay between an ON and an OFF channel. The formation of this wiring dichotomy is not understood. Two neuropil sublayers of the inner plexiform layer (IPL) represent levels of cholinergic synaptic circuitry. These two sublayers are better segregated in avians than in most vertebrates; in the chick they are called a and d and participate in the OFF and ON channel, respectively. Both levels can be detected easily in the mature retina by choline acetyltransferase (ChAT) or by acetylcholinesterase (AChE); however, the usefulness of these enzymes as developmental markers is restricted, since ChAT is detected too late, while AChE labels not only cholinergic neuropil. To establish that individual AChE+ cells indeed project into cholinergic subbands a or d (and thus are involved in either channel), in the first part of this study we used the AChE-specific monoclonal antibody 1A2 plus confocal microscopy. We show that at embryonic stage E17 two AChE+ cell types of the inner nuclear layer project into the cholinergic subband a, and another one projects into d. Moreover, two others project into noncholinergic subbands, b and c, which develop only from E14 onwards. In contrast to immunocytochemistry, sensitive AChE histochemistry allows us to trace back the establishment of subbands a and d before E10, with the first AChE subband appearing along with IPL differentiation at E7. The establishment of AChE subbands is preceded by butyrylcholinesterase subbands; with differentiation following a central-peripheral gradient. Since synapses do not develop before E12 in the chick, we conclude that retinal ON-OFF dichotomy is laid down long before the formation of chemical synapses.
Acetylcholinesterase↗
Elevated sulfatide excretion in compound heterozygotes of metachromatic leukodystrophy and ASA-pseudodeficiency allele.
OBJECTIVE: Use of sulfatide excretion in differentiating MLD/PD-heterozygotes from MLD-patients and PD/PD-homozygotes. DESIGN AND METHODS: Sulfatide was extracted from urine sediment with chlorotom/methanol (2:1, v/v). The quantity of sulfatide was measured densitometrically (lambda = 580 nm) after thin-layer chromatography. ASA and beta-galactosidase activities were assayed enzymatically. RESULTS: MLD/PD-heterozygotes excreted sulfatide in the range of 4.8-36.3 nmol/mg lipid (mean +/- SD = 17.8 +/- 10.7), whereas sulfatide in MLD-patients ranged from 74.3-411.6 nmol/mg lipid (mean +/- SD = 184.5 +/- 130.8) and in PD/PD-hormozygotes sulfatide excretion remained in normal range of 0.0-5.9 nmol/mg lipid (mean +/- SD = 1.64 +/- 2.12). ASA activities in these groups were very low or lowered. CONCLUSIONS: The quantitative measurement of sulfatide in urine allows differentiation between MLD/PD-heterozygotes and MLD-heterozygotes, as well as between MLD/PD-heterozygotes with very low ASA activity and MLD-patients or PD/PD-hormozygotes. The quantitative measurement of sulfatide in urine differs between MLD-carriers and controls.
Adolescent↗
Case report: thickening of the walls of non-dilated bile ducts.
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Adult↗
Inhaled nitric oxide in patients with critical pulmonary perfusion after Fontan-type procedures and bidirectional Glenn anastomosis.
OBJECTIVE: The aim of this study was to evaluate the effects of inhaled nitric oxide in patients with critical pulmonary perfusion after Fontan-type procedures and bidirectional Glenn anastomosis. METHODS: Inhaled nitric oxide (mean 4.1 +/- 0.7 ppm, 1.5 to 10 ppm) was administered in 13 patients (mean age 5.6 +/- 1.6 years, 1.5 to 17 years) with critical pulmonary perfusion (central venous pressure > 20 mm Hg or transpulmonary pressure gradient > 10 mm Hg) in the early postoperative period after total cavopulmonary connection (n = 9) or after bidirectional Glenn anastomosis (n = 4). RESULTS: In patients after total cavopulmonary connection inhaled nitric oxide therapy decreased central venous pressure by 15.3% +/- 1.4% (p = 0.0001) and transpulmonary pressure gradient by 42% +/- 8% (p = 0.0008) and increased mean systemic arterial and left atrial pressures by 12% +/- 3.6% (p = 0.011) and 28% +/- 8% (p = 0.007), respectively. Arterial and venous oxygen saturations improved by 8.2% +/- 1% (p = 0.005) and 14% +/- 4.3% (p = 0.03), respectively. In patients after bidirectional Glenn anastomosis inhaled nitric oxide therapy resulted in a decrease of central venous pressure by 22% +/- 1% and of the transpulmonary pressure gradient by 55% +/- 6% and improved arterial and venous oxygen saturations by 37% +/- 29% and 11% +/- 3%, respectively. Mean systemic arterial and left atrial pressures remained nearly unchanged. No toxic side effect was observed in any patient. CONCLUSION: Inhaled nitric oxide may play an important role in the management of transient critical pulmonary perfusion caused by reactive elevated pulmonary vascular resistance in the early postoperative period after Fontan-type operations and bidirectional Glenn anastomosis.
Administration, Inhalation↗
Efficacy of antihistamine pretreatment in the prevention of adverse reactions to Hymenoptera immunotherapy: a prospective, randomized, placebo-controlled trial.
BACKGROUND: Some clinical studies suggest that a combination of an H1- and H2-antagonist may be effective in the prophylaxis of allergic reactions. OBJECTIVE: The efficacy of pretreatment with an H1/H2-antagonist combination, H1-antagonist alone, or placebo in the prophylaxis of local and systemic adverse reactions to specific immunotherapy with Hymenoptera venom was compared. METHODS: In a prospective, randomized, double-blind, placebo-controlled study, 121 patients with Hymenoptera venom allergy were treated with rush immunotherapy and pretreatment with one of the following: 120 mg of terfenadine plus 300 mg of ranitidine, 120 mg of terfenadine alone, or placebo. The incidence of unwanted systemic adverse and local reactions was recorded for up to 50 weeks. RESULTS: In seven patients (6%), six in the placebo group and one in the terfenadine group, systemic side effects required cessation of therapy (p = 0.005). Subjective symptoms occurred in four patients (10%) in the terfenadine plus ranitidine group and in three patients (7%) in the terfenadine group. Regarding local reactions, significantly fewer patients treated with a combination of terfenadine and ranitidine and with terfenadine alone as compared with placebo had severe local symptoms of erythema (29%, 29%, and 49%), edema (24%, 18%, and 41%), and pruritus (13%, 11%, and 31%) at week 1 (p < 0.05). This therapeutic benefit was limited to the first 4 weeks of treatment. Treatment with a combination of terfenadine and ranitidine was not superior to treatment with terfenadine alone. CONCLUSIONS: Pretreatment with H1-antihistamines with or without H2-antihistamines significantly reduced local and systemic adverse reactions to immunotherapy with Hymenoptera venom and may therefore be helpful in the management of immunotherapy.
Administration, Oral↗
Human leukocyte antigens and cytokine expression in cerebral inflammatory demyelinative lesions of X-linked adrenoleukodystrophy and multiple sclerosis.
The two most common forms of X-linked adrenoleukodystrophy (X-ALD) are the cerebral forms (CER) with an inflammatory demyelinating reaction that resembles multiple sclerosis, and adrenomyeloneuropathy (AMN) which involves primarily the spinal cord and in which the inflammatory reaction is mild or absent. We found no significant association between the childhood cerebral form (CCER) or AMN and the human leukocyte (HLA) class I and Class II antigens including the class II DR2 haplotypes associated with multiple sclerosis. Inflammatory cytokine (tumor necrosis factor-alpha, interleukin-1 beta, interleukin-4, interleukin-6 and interferon-gamma) gene expression was increased in multiple sclerosis brain lesions, as has been reported previously, but much less so in CER brain lesions. These findings suggest that the pathogenesis of the inflammatory response in X-ALD differs from that in multiple sclerosis.
Adrenoleukodystrophy↗
Weekly iron supplementation is as effective as 5 day per week iron supplementation in Bolivian school children living at high altitude.
OBJECTIVE: To compare the efficacy of a daily and a weekly iron supplementation on the hematological status of anemic children living at high altitude. DESIGN: Double blind iron supplementation trial including a placebo control group. SETTING: A socioeconomically disadvantaged district of La Paz, Bolivia (altitude of 4000 m). SUBJECTS: Anemic (hemoglobin concentration < or = 144 g/L), 3.3-8.3 y old children of both sexes. INTERVENTION: Children received a placebo (n = 57) or a dose of 3-4 mg of elemental iron per kg body weight (FeSO4 tablets) 1 d per week (n = 58) or 5 d per week (n = 58) for 16 weeks. RESULTS: Hemoglobin and zinc erythrocyte protoporphyrin concentrations improved significantly in supplemented groups but not in the placebo group. Changes in hemoglobin during the study were not significantly different between supplemented groups (weekly group: 15.2 +/- 6.9 g/L and daily group: 18.6 +/- 11.1 g/L) but were different from the placebo group (0.5 +/- 7.1 g/L, P < 0.001). At the end of the supplementation period, the hemoglobin distribution was Gaussian, and similar in both supplemented groups. Adjusting for the initial hemoglobin concentration, final hemoglobin and its changes were similar in both supplemented groups. CONCLUSION: Weekly iron supplementation is as efficacious as daily iron supplementation in improving iron status and correcting moderate iron deficiency anemia in Bolivian school children living at high altitude. SPONSORSHIP: Program supported in part by ORSTROM, the French Ministry of Foreign Affairs and the National Secretary's Office of Health, Bolivia.
Altitude↗
Widespread dissemination of a drug-susceptible strain of Mycobacterium tuberculosis.
In New York City, a large proportion of new tuberculosis cases has been caused by 1 drug-susceptible strain (called C strain) of Mycobacterium tuberculosis. Between 1991 and 1994, among >600 tuberculosis patients consecutively identified in four large hospitals in the city, 54 with C strain, 69 with non-C cluster pattern strains, and 42 with noncluster pattern strains were studied. Susceptibility to reactive nitrogen intermediates (RNI) of selected isolates was compared. In a case-control analysis, 51% of patients with C strain, 28% with non-C cluster strains (P < .05), and 14% with noncluster strains (P < .01) were found to be injection drug users. C strain but not 13 other unrelated isolates were resistant to RNI. Injection drug use may provide a selective pressure for an RNI-resistant tubercle bacillus to emerge, which may give the organism a biologic advantage and explain the widespread dissemination of C strain M. tuberculosis within the city.
Adolescent↗
A high-resolution esophageal electrocardiogram for monitoring atrial activity in the hypothermic potassium-arrested heart.
Atrial electrical activities during hypothermic, K(+)-induced cardioplegic arrest correlate with an increased incidence of postoperative supraventricular dysrhythmias in coronary artery bypass graft patients. Surface electrocardiogram (ECG) (S-ECG) may be insufficiently sensitive to detect such activity intraoperatively, and invasive methods are impractical and traumatic. From induction of anesthesia until the end of surgery, esophageal ECG signals were detected with a new bipolar esophageal probe and a new high-resolution preamplifier (frequency range 0.01-2000 Hz). The S-ECG and the esophageal ECG (E-ECG) were evaluated independently in 18 patients. Eight of 18 patients presented during cardioplegic arrest a mean of 483 +/- 119 high-amplitude, biphasic P components (mean amplitude 0.7 +/- 0.1 mV, range 0.35-1.15 mV) per patient (mean 36 +/- 6 [5-59] potentials/min) similar to those coinciding with the surface ECG P-waves during sinus rhythm. Six of these eight patients presented a mean of 29 +/- 11 low atrial activities (mean amplitude 0.14 +/- 0.023 mV; range 0.1-0.25 mV) per patient (mean 8.4 +/- 5.6 [2.3-48] potentials/min) in the E-ECG. In the S-ECG, one patient of these eight presented 26 P waves during cardioplegic arrest simultaneously with activities in the E-ECG. During the first 5 days, seven of eight (88%) patients with atrial activities in the E-ECG versus 3 of 10 (30%) patients without atrial activities developed supraventricular tachyarrhythmias postoperatively (P < 0.05). This new high-resolution E-ECG device detected in a beat-to-beat technique more atrial activity during cardioplegic arrest than a S-ECG and offered the advantages of artifact exclusion and better prediction of postoperative supraventricular dysrhythmias.
Aged↗
Selective intestinal decontamination in multiple trauma patients: prospective, controlled trial.
BACKGROUND: Reduction of potential pathogens by selective intestinal decontamination has been proposed to improve intensive care. Despite large scientific interest in this method, little is known about its benefit in homogeneous trauma populations. METHODS: In a prospective, controlled study, we enrolled non-infected trauma patients (age over 18 years, mechanical ventilation > or = 48 hours, intensive care for more than 3 days) who primarily were admitted to our university medical center. We randomized patients to be treated with two different topical regimens (polymyxin, tobramycin, and amphotericin (PTA) or polymyxin, ciprofloxin, amphotericin (PCA)) or the carrier only (placebo), administered four times daily both to the oropharynx and to the gastrointestinal tract. All patients received intravenous ciprofloxacin (200 mg, bd) for 4 days. FINDINGS: Of 357 enrolled patients, 310 (age 38.0 +/- 16.5 years, Injury Severity Score 35.2 +/- 12.7) met all inclusion criteria. Selective decontamination successfully reduced intestinal bacterial colonization. However, we did not identify significant differences between groups regarding pneumonia (PTA 47.5%, PCA 39.0%, placebo 45.3%), sepsis (PTA 47.5%, PCA 37.8%, placebo 42.6%), multiple organ failure (PTA 56.3%; PCA 52.4%, placebo 58.1%), and death (PTA 11.3%, PCA 12.2%, placebo 10.8%). Total costs per patient were highest with the PTA regimen. CONCLUSIONS: We found no benefit of selective decontamination in trauma patients. Apparently, bacterial overgrowth in the intestinal tract is not the sole link between trauma, sepsis, and organ failure.
Adult↗
Definition and prevalence of anemia in Bolivian women of childbearing age living at high altitudes: the effect of iron-folate supplementation.
This paper discusses the effect that high altitudes have on iron metabolism and summarizes the results of an iron-folate supplementation trial. The two main objectives of the trial were to determine hemoglobin cut-off values for the diagnosis of anemia in Bolivian women of childbearing age living at high altitudes, and to estimate the prevalence of anemia in this population. The study showed that nutritional anemia is an important public health problem in such populations and that many methods of assessing it lead to an underestimation of prevalence. The cut-off values defined through this study, one of the few iron supplementation trials conducted at high altitudes, confirm the need to establish revised hemoglobin values for the diagnosis of anemia in populations living at high altitudes.
Adolescent↗
Increased risk for opportunistic infections during chemotherapy in HIV-infected patients with Kaposi's sarcoma.
BACKGROUND: Kaposi's sarcoma (KS) is the most frequent neoplasm in patients with AIDS, responsible for death in about 20-30% of the affected patients. OBJECTIVE: To determine the frequency of opportunistic infections (OI) and change of CD4+ cell counts in patients with KS treated with chemotherapy compared to a group of matched-pair patients without chemotherapy. METHODS: In a prospective study, the clinical courses of 35 HIV-infected patients with KS treated with chemotherapy were compared with 35 matched-pair patients without chemotherapy. RESULTS: During the observation period of 6 months, 11 OI occurred in 10 patients of the chemotherapy group and 5 OI in 5 patients of the control group. With respect to the changes of CD4+ cell counts, no significant differences could be observed. CONCLUSION: The risk for OI in HIV-infected patients with KS is increased while receiving chemotherapy. This should be reflected upon when chemotherapy is taken into consideration.
AIDS-Related Opportunistic Infections↗