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Biomedical subjects

M Klein

Publications and source records attributed to M Klein.

At least 217 records · Page 12Linked to original sources
PubMed1998

Lead poisoning secondary to hyperthyroidism: report of two cases.

With long-term exposure to lead, lead accumulates in bone, where it is stored for years. These quiescent lead stores are mobilised when increased bone turnover occurs, and latent lead toxicity may then become symptomatic. Although Graves' disease is a common cause of increased bone turnover, to date hyperthyroidism has been implicated in lead poisoning only twice. We describe herein two cases of hyperthyroidism, one caused by toxic multinodular thyroid enlargement, the second by Graves' disease, leading to lead poisoning. Treatment of hyperthyroidism with radioactive iodine cured both hyperthyroidism and lead poisoning and no chelating agent therapy was necessary. Lead poisoning is an important environmental health problem, and physicians must be aware of the endocrine disorders such as hyperthyroidism and hyperparathyroidism that increase bone turnover, favouring lead mobilisation. Atypical symptoms should draw the physician's attention to the possibility of lead poisoning, particularly in workers with occupational exposure to lead and in areas where lead poisoning is endemic.

Adult↗
PubMed1998

An in vitro comparison of the computerized tomography/CAD-CAM and direct bone impression techniques for subperiosteal implant model generation.

Subperiosteal implants are currently fabricated by using the classic two-stage direct bone impression technique or by the use of the one-stage computer tomography/computer-assisted design-computer-assisted manufacture (CT/CAD-CAM) method. This study compares the accuracy of the two techniques by using cadaver maxillae and mandibles as the models for fabrication of casts. Seven cadaver jaw specimens were collected and subjected to direct bone impressions and to CT scans. Those derived from the direct bone impressions were poured in die stone, while the CT scans were sent for fabrication of CAD-CAM-generated casts. On each of the 14 models so produced, a cast grid was fabricated that was designed as a measuring device. The preciseness of fit of each grid was subjected to analyses that presented levels of accuracy. Statistical evaluation of these levels, reduced to numerical indices, revealed that the direct bone techniques resulted in acceptable castings in seven of seven cases, whereas the CAD-CAM method yielded adequate castings in five of seven cases.

Computer-Aided Design↗
PubMed1998

Congenital diaphragmatic hernia survival and use of extracorporeal life support at selected level III nurseries with multimodality support.

BACKGROUND: Congenital diaphragmatic hernia (CDH) has been cited to have a mortality rate of 50%. There have been multiple studies at individual institutions demonstrating potential benefits from various strategies including extracorporeal life support (ECLS), delayed repair, and lower levels of ventilator support. There has been no multicenter survey of institutions offering these modalities to describe the current use of ECLS and survival of these infants. In addition, the relationship between the number of patients with CDH managed at an individual institution and outcome has not been evaluated. METHODS: We queried 16 level III neonatal intensive care centers on the use of ECLS and survival of infants with CDH who were treated during 2 consecutive years (1993 to 1995). Data are presented as mean +/- SEM, median, and range. RESULTS: Data were collected on 411 patients. Of these, 71% +/- 8% were outborn and 8% +/- 3% were considered nonviable. Overall survival of CDH infants was 69% +/- 4% (range, 39% to 95%). The survival rate of infants on ECLS was 55% +/- 4%, whereas survival of infants not requiring ECLS was significantly increased at 81% +/- 5% (p = 0.005). The mean rate of ECLS use was 46% +/- 2%. There was no correlation between the number of cases per year at an individual institution and overall survival, ECLS survival, or ECLS use (r = 0.341, 0.305, and 0.287, respectively). There was also no correlation between case volume at an individual institution and ECLS survival (r = 0.271). CONCLUSIONS: The current survival rate and rate of ECLS use in infants with CDH at level III neonatal intensive care units in the United States are 69% +/- 4% and 46% +/- 2%, respectively. There is no correlation between the yearly individual center experience with managing CDH and rate of ECLS use or outcome.

Extracorporeal Circulation↗
PubMed1998

Enzyme replacement therapy decreases hypergammaglobulinemia in Gaucher's disease.

We report the effects of enzyme replacement therapy in a patient with Gaucher's disease associated with a monoclonal gammopathy. Alglucerase induces a linear decline in immunoglobulin and beta 2-microglobulin levels. This observation suggests that this treatment decreases the chronic antigenic stimulation commonly found in Gaucher's disease.

Adult↗
PubMed1998

Mitral valve repair: Intermediate to long-term echocardiographic follow-up.

OBJECTIVE: To review intermediate to long term echocardiographic follow-up after mitral valve repair for mitral regurgitation. DESIGN: Nonrandomized, retrospective and prospective observational study. SETTING: Sacré-Coeur Hospital, University of Montreal, Montreal, Quebec. PATIENTS: Echocardiographic findings in 37 patients (mean age 62.1 +/- 10 years) three to 197 months (median 45) after mitral valve repair were reviewed. INTERVENTIONS: Preoperative data were collated from hospital records. Between October 1994 and March 1995, all patients had a clinical evaluation and a complete transthoracic echocardiogram done by a cardiologist. RESULT: There was a significant reduction in the dimensions of the left-sided cavities compared with preoperative data. Left atrial diameter decreased from from 50.9 +/- 7.7 to 46.3 +/- 8.1 mm (P = 0.01), left ventricular end-diastolic diameter from 59.6 +/- 7.1 to 51.2 +/- 6.3 mm (P < 0.001) and left ventricular end-systolic diameter from 35.3 +/- 7.9 to 32.8 +/- 7.8 mm (P = 0.07). On colour Doppler echocardiography, nine patients had no mitral regurgitation, 25 had mitral regurgitation grade I to II/IV, and three had grade III/IV. The mean mitral valve gradient was 4.2 +/- 1.8 mmHg and the pressure half-time 121.9 +/- 48 ms. There was no difference in gradient, mitral valve area and mitral regurgitation in patients with degenerative (29) compared with rheumatic (five) mitral valve disease. CONCLUSIONS: Mitral valve repair is highly effective in reducing mitral regurgitation in the long term and is associated with a reduction in the dimensions of the left atrium and the left ventricle. However, it leaves a mild degree of mitral valve obstruction.

Aged↗
PubMed1997

Transport of lucifer yellow CH into plant vacuoles--evidence for direct energization of a sulphonated substance and implications for the design of new molecular probes.

Contrasting observations exist which indicate that in plants the fluorescent dye lucifer yellow CH (LYCH) either can be used as a tracer for endocytosis or as a substrate for an anion transporter located at the vacuolar membrane. In addition, LYCH as a disulphonated substance may represent an analogue of sulphonated or sulfated natural compounds like some flavonoids. We performed uptake experiments with LYCH into isolated rye vacuoles and observed saturable (Km = 0.3-0.6 mM) vacuolar transport and accumulation of the dye against the concentration gradient only when MgATP was present. GTP and, to a low extent, UTP could substitute for ATP, while the non-hydrolysable ATP analogue AMP-PNP did not drive LYCH uptake. Vanadate and probenecid, the latter substance is known to inhibit organic anion transport at the liver canalicular membrane, both strongly decreased the vacuolar uptake of LYCH, while bafilomycin A1, a specific inhibitor of the vacuolar H+-ATPase, had no effect. Together with the fact that abolishment of the delta pH via CCCP had only a weak influence on LYCH accumulation, our results indicate that this compound is taken up into rye vacuoles by a directly energized process. Uptake of LYCH was strongly inhibited by other sulfated compounds including sulfobromophthalein and the flavones apigenin 7,4'-disulfate and luteolin 7,4'-disulfate arguing for the presence of a vacuolar transporter for structurally different sulphonated or sulfated compounds. Glucuronates like the rye-specific flavone luteolin 7-O-diglucuronide also strongly decreased uptake of the dye, whereas only a weak effect was observed in the presence of glutathione and a glutathione conjugate, suggesting that LYCH uptake is not mediated via the vacuolar glutathione conjugate pump.

ATP-Binding Cassette Transporters↗
PubMed1997

A controlled trial of isoniazid in persons with anergy and human immunodeficiency virus infection who are at high risk for tuberculosis. Terry Beirn Community Programs for Clinical Research on AIDS.

BACKGROUND: Patients with human immunodeficiency virus (HIV) infection and latent tuberculosis are at substantial risk for the development of active tuberculosis. As a public health measure, prophylactic treatment with isoniazid has been suggested for HIV-infected persons who have anergy and are in groups with a high prevalence of tuberculosis. METHODS: We conducted a multicenter, randomized, double-blind, placebo-controlled trial of six months of prophylactic isoniazid treatment in HIV-infected patients with anergy who have risk factors for tuberculosis infection. The primary end point was culture-confirmed tuberculosis. RESULTS: The study was conducted from November 1991 through June 1996. Over 90 percent of the patients had two or more risk factors for tuberculosis infection, and nearly 75 percent of patients were from greater New York City. After a mean follow-up of 33 months, tuberculosis was diagnosed in only 6 of 257 patients in the placebo group and 3 of 260 patients in the isoniazid group (risk ratio, 0.48; 95 percent confidence interval, 0.12 to 1.91; P=0.30). There were no significant differences between the two groups with regard to death, death or the progression of HIV disease, or adverse events. CONCLUSIONS: Even in HIV-infected patients with anergy and multiple risk factors for latent tuberculosis infection, the rate of development of active tuberculosis is low. This finding does not support the use of isoniazid prophylaxis in high-risk patients with HIV infection and anergy unless they have been exposed to active tuberculosis.

AIDS-Related Opportunistic Infections↗
PubMed1997

Conversion of recurrent delta-positive hepatitis B infection to seronegativity with famciclovir after liver transplantation.

BACKGROUND: Recurrent hepatitis B infection after liver transplantation is associated with poor graft and patient survival. Famciclovir is a nucleoside with virostatic action in hepatitis B infection. We report the case of a 51-year-old patient who developed recurrent delta-positive hepatitis B infection after liver transplantation. After famciclovir treatment, he became seronegative for hepatitis B early and hepatitis B surface antigens and developed protective anti-hepatitis B surface antibody titers. METHODS: After recurrent hepatitis B was confirmed, treatment with famciclovir was initiated. RESULTS: Eighteen days after starting famciclovir, the patient became seronegative for hepatitis B early antigen and delta antigen, and hepatitis B virus DNA was no longer detectable in serum. Three months later, the patient became hepatitis B surface antigen negative and remains well 16 months later with increasing anti-hepatitis B surface levels. CONCLUSIONS: Antiviral treatment with famciclovir may be useful in treatment of delta-positive hepatitis B infection following liver transplantation. Further evaluation of famciclovir in treatment and prevention of hepatitis B in these patients is warranted.

2-Aminopurine↗
PubMed1997

Functional interactions in cytochrome P450BM3: flavin semiquinone intermediates, role of NADP(H), and mechanism of electron transfer by the flavoprotein domain.

Cytochrome P450BM3 is a self-sufficient soluble fatty acid hydroxylase from Bacillus megaterium utilizing tightly bound FAD and FMN cofactors to transfer reducing equivalents from NADPH to the heme active site. Active-inactive transitions of cytochrome P450BM3 were exploited to identify catalytic intermediates of the enzyme. Shortly upon reduction by NADPH, a two-electron reduced active P450BM3 is formed with two flavin semiquinones, anionic and neutral, present simultaneously. P450BM3 inactivated by NADPH has a three-electron reduced flavoprotein domain. NADPH is unable to reduce P450BM3 rapidly unless the flavoprotein domain is fully oxidized. During steady-state hydroxylation of a poor substrate, tetradecanol, the flavoprotein reduction state does not exceed two, with two flavin semiquinones, anionic and neutral, present. Absorbance and EPR spectroscopic characterization of both anionic and neutral flavin semiquinone is presented. NADPH and NADH were compared as electron donors for P450BM3-catalyzed fatty acid hydroxylation and cytochrome c and heme iron reduction. The Km for NADH of 3-5 mM is about 3000 times higher than the Km of 1-1.5 microM for NADPH. Although NADH can support cytochrome c reduction and fatty acid hydroxylation with the rates as high as 22 and 13 s-1, respectively, these turnover numbers are only about 20% of those observed with NADPH. The results suggest that nucleotide binding plays an important role in catalysis by controlling electron-transfer properties of the flavin cofactors. In W574G and G570D mutant P450BM3 enzymes that are deficient in FMN, NADP+ binding stabilizes fully reduced FAD. P450BM3 catalyzes single-turnover and steady-state laurate hydroxylation with near stoichiometric product formation at NADPH concentrations below that of the enzyme. A mechanism of electron transfer by the flavoprotein domain of P450BM3 is proposed with the reduction state of the flavoprotein domain cycling in a 0-2-1-0 sequence. We also propose that an interaction of bound NADP+ with anionic FAD semiquinone is essential for splitting a pair of electrons that are then transferred in two one-electron transfer steps to the heme catalytic site.

Bacillus megaterium↗
PubMed1997

Analysis of the lipidated recombinant outer surface protein A from Borrelia burgdorferi by mass spectrometry.

The outer surface protein A, OspA, from the spirochete Borrelia burgdorferi is a lipoprotein of 25 kDa. The recombinant OspA (rOspA) expressed in Escherichia coli has been purified and analyzed by electrospray mass spectrometry (ESMS). A heterogenous spectrum gave a measured mass of 28,462 +/- 9 Da for the major component compared to an expected mass of 28,445 Da (Deltam = +17 Da), and a measured mass of 28,228 +/- 7 Da for a minor component. The theoretical mass is based on the N-terminal being an S-[2,3-bis(palmitoyloxy)-(2R, S-[2,3-bis(palmitoyloxy)-(2R,S)-propyl]-N-palmitoylcysteine modification according to the model established by Hantke and Braun (Eur. J. Biochem. 34, 284-296, 1973) for bacterial lipoproteins. To determine whether rOspA conforms to this model, a complementary detailed analysis of this lipidation was necessary. The fatty acid content of the complete protein as analyzed by gas chromatography-mass spectrometry revealed saturated fatty acids ranging from C14 to C18 as well as C16 and C18 unsaturated fatty acids, with palmitate (C16:0) being the major component. Focusing on the lipid moieties, the N-terminal tryptic peptide was purified by normal phase HPLC using a silica column and a gradient of hexane in isopropanol. Analysis of the N-terminal peptide by ESMS and fast atom bombardment-mass spectrometry revealed a minor fraction of rOspA molecules which contained only two C16 residues and that in addition to partial oxidation, the major N-terminal peptide had a mass difference of -2 Da compared to a theoretical structure with three palmitate residues, indicating that one of the three fatty acid residues was unsaturated. Minor forms with mass differences of 28 Da were also observed, indicating that one of the three acyl residues was C14 in one case and C18 in the other, instead of C16 in the major form. Analysis of the rOspA peptide backbone revealed that the sole methionine at position 22 was partially oxidized to a methionine sulfoxide. Thus the mass analysis of the major mass is consistent with a mixed population of lipoprotein molecules containing variations not only in the lipid moiety contributing to an elevation in the mass of Deltam = 7 Da compared to the theoretical structure proposed, but also in the peptide chain. Partial oxidations at two points in the protein backbone (<30% of the population in each case) contribute to an additional augmentation in mass and thus can account for the remaining mass difference in the measured mass.

Amino Acid Sequence↗
PubMed1997

Treatment of chronic hepatitis C with consensus interferon: a multicenter, randomized, controlled trial. Consensus Interferon Study Group.

This multicenter, randomized, controlled, double-blind, phase III study in 704 patients with chronic hepatitis C infection compared treatment with consensus interferon (CIFN), a non-natural recombinant type-1 interferon, with a standard regimen of recombinant interferon alfa-2b (IFN-alpha2b). Patients were randomized to receive CIFN at doses of 3 microg or 9 microg, or 15 microg IFN-alpha2b (3 million units), subcutaneously three times weekly for 24 weeks, followed by 24 weeks of observation. Efficacy was assessed by normalization of serum alanine transaminase (ALT) concentration and decrease in serum hepatitis C virus (HCV) RNA concentration below the limit of detection by reverse-transcription polymerase chain reaction (RT-PCR) (100 copies/mL). The beneficial effect of CIFN was greater with the 9-microg dose than the 3-microg dose. The sustained ALT and HCV RNA response rates were 20.3% and 12.1%, respectively, in the 9-microg CIFN cohort and 19.6% and 11.3%, respectively, in the 15-microg IFN-alpha2b cohort. However, patients receiving 9 microg of CIFN had a greater reduction in serum HCV RNA concentrations compared with patients receiving 15 microg IFN-alpha2b over the course of treatment (P < .01). Similarly, analysis of patients infected with HCV genotype 1 showed a greater reduction in serum HCV RNA concentration over the course of treatment for the 9-microg CIFN group when compared with the 15-microg IFN-alpha2b group (P < .01). In addition, a greater percentage of patients infected with HCV genotype 1 treated with 9 microg CIFN had undetectable HCV RNA concentrations when compared with patients in the 15-microg IFN-alpha2b cohort at the end of treatment (24% vs. 15%; P = .04). Improvements in liver histology were noted in all three treatment groups; 52% to 55% of the patients in the three cohorts had at least a 2-unit improvement in the Knodell score at the end of the posttreatment period. The adverse-events profiles were characteristic of treatment with type-1 interferon, and the incidences of anti-interferon antibody formation did not significantly differ among the three treatment groups. These results show that administration of 9 microg CIFN three times weekly for 6 months is safe and is effective in reducing serum HCV RNA concentration.

Adult↗