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Biomedical subjects

H Falk

Publications and source records attributed to H Falk.

At least 37 records · Page 2Linked to original sources
PubMed1996

The natural history of eosinophilia-myalgia syndrome in a tryptophan-exposed cohort in South Carolina.

BACKGROUND: In a previous study, we did follow-up on 418 patients who were exposed to tryptophan in 1989, of whom 47 (11%) had definite and 63 (9%) possible eosinophilia-myalgia syndrome (EMS). METHODS: We assessed mortality and clinical spectrum of illness since 1989 for 242 (58%) of the 418 tryptophan-exposed patients from the original study. To assess outcomes, we used hospital and death records, interviewer-administered questionnaires, physical examinations, and laboratory tests. RESULTS: During the follow-up interval, mortality from all causes was 19% in those with definite EMS, 7% in possible EMS, and 3% in those who were not ill. The age- and sex-adjusted mortality in those with definite EMS was more than 3 times that of the general population or of tryptophan users in the practice who were not ill. Six deaths (66%) among the definite EMS case patients occurred during the 18 months immediately after symptom onset. Compared with the tryptophan users who were not ill, survivors with definite EMS continued to report excess morbidity for 6 major EMS symptoms (myalgia, arthralgia, weakness, rash, alopecia, and sclerodermiform skin changes), but they also reported that the symptom number and severity diminished with time. None of the tryptophan users who were not ill in 1989 developed a symptom complex suggesting new EMS during the follow-up interval. CONCLUSIONS: This study assessing a tryptophan-exposed population found those persons who developed EMS during the 1989 epidemic were at increased risk for death, particularly early after disease onset. Survivors reported improvement or resolution of major symptoms, suggesting that the severity of EMS diminishes with time. We found no evidence of delayed onset of EMS in tryptophan users who were not ill in 1989, regardless of the brand used.

Drug Contamination↗
PubMed1996

Tryptophan produced by Showa Denko and epidemic eosinophilia-myalgia syndrome.

Evidence from an array of scientific studies strongly supports the conclusion that ingestion of products containing L-tryptophan (LT) produced by Showa Denko KK caused the 1989 epidemic of eosinophilia-myalgia syndrome (EMS) in the United State. In case-control studies of EMS, LT exposure was essentially universal among cases but rare among controls. Of 6 manufacturers of LT, only LT manufactured by Showa Denko KK was clearly associated with illness. The data meet other Hill criteria for inferring a causal relationship. Consistent findings were found in multiple independently conducted studies. There was a dose-response effect, with risk of illness increasing as a function of the amount of tryptophan consumed. The extremely small p values observed in the multiple independently conducted studies effectively rule out the possibility that the tryptophan-EMS association was the result of chance. Moreover, no potential confounding factor or bias explains the association. The incidence of EMS in the United States diminished abruptly once LT containing products were recalled.

Drug Industry↗
PubMed1995

Translation efficiency of the human T-cell leukemia virus (HTLV-2) gag gene modulates the frequency of ribosomal frameshifting.

The regulation of ribosomal frameshifting during translation of the polycistronic mRNA of human T-cell leukemia virus (HTLV) was studied in a cell-free system. Translation inhibitors such as cycloheximide and puromycin antibiotics were much more effective in blocking the synthesis of the frameshift polypeptide Gag-Pro than the synthesis of the Gag product. The preferential inhibition of the frameshift polypeptide Gag-Pro by the two antibiotics was not a reflection of the different sizes of the two gene products, but rather a consequence of the effect of the inhibitors on ribosomal translation efficiencies. To further analyze the effect of translation efficiencies on ribosomal frameshifting, we compared the translation of 5'-capped RNA to noncapped RNA. The translation of 5'-capped RNA was higher, as expected. Consequently, ribosomal frameshifting producing the Gag-Pro polypeptide was enhanced when compared to the translation of noncapped RNA. Taken together these results indicate that efficiencies of translation, in conjunction with the cis regulatory genetic elements at the frameshift sites, determine the ratio of the polypeptides Gag, Gag-Pro, and Gag-Pro-Pol produced in the HTLV-infected cell. Thus, physiological changes which affect the cellular translation machinery may alter the optimal ratio of these three polyprotein products needed for virus maturation.

Cell-Free System↗
PubMed1995

Structure determination of the biliverdin apomyoglobin complex: crystal structure analysis of two crystal forms at 1.4 and 1.5 A resolution.

Crystal structure determinations of two orthorhombic (P2(1)2(1)2(1)) crystal modifications of the biliverdin apomyoglobin complex are described. The two structures were determined by X-ray diffraction at 100 K to a resolution of 1.5 A and 1.4 A. Both crystal forms were grown by hanging-drop techniques, using phosphate as precipitant. The structures were solved by molecular replacement and refined to final R-values of 19.4% and 21.2%. Both structures are very similar with respect to the binding site and the conformation of the biliverdin chromophore, which occurs in a (P) helical conformation. It is located within the heme pocket, very close in position and orientation to the heme binding site in myoglobin. Two water molecules not present in the crystal structure of myoglobin are sequestered within the heme pocket in the biliverdin-apomyoglobin complex, and they are engaged in hydrogen bonding to the biliverdin and to the protein. Comparison with structural results from an earlier NMR study of the same complex shows good agreement.

Apoproteins↗
PubMed1995

Subclinical health effects in a population exposed to excess vitamin D in milk.

To evaluate subclinical health effects of excess vitamin D, a cross-sectional study was conducted of persons consuming milk from a dairy that had overfortified milk for at least 4 years. Milk consumption, sunlight exposure, medical symptoms, serum 25-hydroxyvitamin D (25[OH]D), serum and urinary calcium, and indicators of renal function were measured. Increased milk consumption was associated with increased serum 25(OH)D and urinary calcium. However, the prevalences of elevated serum 25(OH)D and calcium were no greater than expected, and data indicated normal renal function. It was concluded that most persons exposed to excess vitamin D exhibited no measurable adverse subclinical effects.

25-Hydroxyvitamin D 2↗
PubMed1995

An outbreak of hypervitaminosis D associated with the overfortification of milk from a home-delivery dairy.

OBJECTIVES: The purpose of the study was to identify cases of hypervitaminosis D caused by the inadvertent overfortification of milk from a home-delivery dairy and to identify risk factors for this illness. METHODS: Hospital discharge, laboratory, and state health department data were used to define, identify, and describe cases of hypervitaminosis D diagnosed in the exposed communities between January 1, 1985, and June 30, 1991. To identify disease risk factors, community-based sex- and age-matched controls were used in a case-control study. RESULTS: Of the 56 case patients identified, at least 41 were hospitalized; 2 died. The study included 33 case patients and 93 control subjects. Nineteen of the 33 case patients had been customers of the implicated dairy. Risk of illness rose with increasing consumption of the dairy's milk and was also associated with vitamin D supplement use, sunburn susceptibility, and cancer history. Accounting for these factors did not alter the association between drinking the dairy's milk and developing hypervitaminosis D. CONCLUSIONS: Overfortification of milk with vitamin D can lead to hypervitaminosis D, manifested by severe illness and death. The episode highlights the need for monitoring the fortification process and enforcing the upper limit for vitamin D addition to milk.

Adolescent↗
PubMed1994

The use of a new bioresorbable barrier for guided bone regeneration in connection with implant installation. Case reports.

This report presents 4 cases with 6 implant exposures after the installation of Brånemark System implants which called for treatment applying the guided bone regeneration technique. A bioresorbable barrier (GUIDOR Matrix Barrier) was used to cover the defects, 4 defects with and 2 without the support of autologous bone chips. Complete bone filling was found in 4 (2 without and 2 with bone chips) and partial filling in 2 (with bone chips) of the treated defects, as registered at the abutment connection 6-7 months after surgery. Besides its ability to serve as a barrier for guided bone regeneration, it was found that the matrix barrier had the following properties; biocompatibility observed as uneventful tissue healing, malleability facilitating the clinical handling and ability to be resorbed within 6 to 7 months, as evaluated by clinical inspection. The observations of the present case reports indicate that the tested barrier may be used for guided bone regeneration in connection with implant installation. It is advisable, however, to use a supporting material to prevent barrier collapse, although bone regeneration can be achieved in certain situations without such material if the defect morphology is favourable.

Aged↗
PubMed1994

Clinical use of a bioresorbable matrix barrier in guided tissue regeneration therapy. Case series.

In this case series study 19 Class II furcations and 47 intrabony defects in 59 patients were treated according to the principles of guided tissue regeneration using a bioresorbable matrix barrier. Gingival condition and device exposure were assessed at 2 weeks, and 1, 3, 6, and 12 months after surgery. The effect of therapy was evaluated by assessing probing depths (PD), probing attachment level (PAL), and the position of the gingival margin prior to surgery and 12 months after surgery. Mild clinical signs of inflammation in the soft tissue covering the device was found adjacent to 3 defects only and limited to the first month of healing. Device exposure occurred at 10 out of the 66 defects. At the furcation defects, the mean PD reduction amounted to 3.7 mm (P < or = 0.001). Mean gain PAL vertical was 3.4 mm and PAL horizontal 3.3 mm (P < or = 0.001), resulting in complete closure of 9 out of the 19 defects. Mean gingival recession was 0.2 mm. At the intrabony defects mean PD reduction was 5.4 mm and mean gain of PAL 4.9 mm (P < or = 0.001). Gingival recession averaged 0.5 mm (P < or = 0.05). It was concluded that the use of the matrix barrier in GTR therapy resulted in 1) reduced probing depths; 2) pronounced gain of clinical attachment; and 3) a very low incidence of gingival pathology, gingival recession, and device exposure.

Adult↗
PubMed1993

Tryptophan contaminants associated with eosinophilia-myalgia syndrome. The Eosinophilia-Myalgia Studies of Oregon, New York and New Mexico.

Eosinophilia-myalgia syndrome (EMS) has been linked to ingestion of tryptophan contaminated with 1,1'-ethylidene-bis[L-tryptophan] (EBT), but other contaminants have received little study. The authors identified 101 lots of L-tryptophan that had been consumed either by persons with EMS or by asymptomatic tryptophan users and quantified the amounts of EBT and five other contaminants in each lot. After stratification of case and noncase lots by time of manufacture to adjust for the strong sequential pattern over time among case and noncase lots, higher EBT levels were still associated with a lot's case status, but the association lacked statistical significance (p = 0.120, odds ratio = 1.56, 95% confidence interval 0.758-3.23). While these findings do not rule out the possibility that EBT is the etiologic agent in EMS, they raise the possibility that other chemical contaminants in manufactured tryptophan modify the effects of EBT or that the causal agent of EMS is an entirely distinct compound.

Drug Contamination↗
PubMed1993

Lowest excited triplet states of hypericin and isohypericin.

The fluorescence and phosphorescence of hypericin and isohypericin were studied in an ethanol matrix at 1.2 K. The prompt fluorescence spectra are mirror images of the absorption around the 0-0 transition, as expected. The 0-0 vibronic lines of the phosphorescence are found at 13,190 and 13,622 cm-1, and the phosphorescence decay times are 2.79 and 6.6 ms at 1.2 K for hypericin and isohypericin respectively. The fluorescence excitation spectrum of isohypericin reveals a small trace of a different pigment, possibly a tautomeric form of isohypericin. The decay of the phosphorescence of isohypericin is biexponential. The slow component is attributed to an unknown contaminant with a high quantum yield of phosphorescence.

Anthracenes↗
PubMed1993

Mortality among people affected by toxic oil syndrome.

The authors conducted a mailed questionnaire survey of a 5% sample of the cohort of 20,643 people officially recognized by the Spanish government as having had toxic oil syndrome, a previously undescribed illness that was epidemic in Spain in 1981. After three mailings of a letter and questionnaire, responses for only 66% of the sample had been received. Nevertheless, responses were obtained from virtually all remaining patients (or surrogates for them in the cases of patients that had died) when they were sought by telephone. In 1981, there was clear-cut excess mortality in the cohort (standardized mortality ratio [SMR] 6.51; 95% confidence interval [CI]: 3.92-10.17). During the period January 1982 through 7 March 1988, there was no statistically significant overall mortality excess except during the period 1982-1983 among people aged < 65 years (SMR 2.26; 95% CI: 1.03-4.29). Toxic oil syndrome substantially altered the patterns of mortality among affected people. Analysis of deaths by cause among the TOS cohort will be useful for further evaluation of the long-term impact of the TOS epidemic.

Adolescent↗
PubMed1993

Two cis-acting signals control ribosomal frameshift between human T-cell leukemia virus type II gag and pro genes.

The open reading frame of the human T-cell leukemia virus type II pro gene is arranged at a -1 position relative to the gag gene. Synthesis of the Gag-Pro fusion polyprotein is facilitated by ribosomal frameshift into the reading frame of the pro gene. Cloning of a synthetic 41-bp oligonucleotide corresponding to the gag-pro junction within a heterologous gene (nef of human immunodeficiency virus type I) and mutation analysis revealed that two cis-acting signals, an adenosine residue stretch and a dyad symmetry sequence, flanking the UAA termination codon, are required for efficient ribosomal frameshifting between gag and pro. The stability of the stem-loop structure is crucial for frameshifting.

Amino Acid Sequence↗
PubMed1993

Eosinophilia-myalgia syndrome: mortality data from the US national surveillance system.

OBJECTIVE: To describe some of the most severe features of eosinophilia-myalgia syndrome (EMS) and identify potential prognostic indicators. METHODS: Systematic review of data from initial case reports and from followup supplemental death report forms forwarded to the national surveillance system administered by the US Centers for Disease Control (CDC). RESULTS: As of August 10, 1991 36 deaths related to EMS had been reported to CDC. Among all patients fitting the surveillance case definition for EMS, we found that patients who died were older, had higher absolute leukocyte and eosinophil counts, and reported a greater frequency of cough or dyspnea, neuropathy, hepatomegaly, leukocytosis, and elevated erythrocyte sedimentation rate. All patients who died had illnesses affecting multiple organ systems. Of the 36 patients who died, 33 (92%) had neuromuscular sequelae, 29 (81%) had pulmonary complications, and 23 (64%) had cardiac manifestations. The most commonly observed disease process leading to death was progressive polyneuropathy and myopathy (24 of the 36 reported deaths) which produced complications of pneumonia and sepsis or respiratory failure due to weakness; cardiomyopathy was the underlying cause of death for 4 patients, primary pulmonary disease for 3, sudden death attributed to arrhythmia for 2, stroke for 2, and septic complications of therapy for one. CONCLUSION: Although neuromuscular complications were the most prominent sequelae among patients reported to have died, this is clearly a multisystemic disease. Older age and involvement of more than one organ system suggest a particularly poor prognosis, and the neuromuscular, pulmonary and cardiovascular sequelae appear to be the most worrisome.

Adult↗
PubMed1992

Survey of advertising for nutritional supplements in health and bodybuilding magazines.

The use of food supplements by the general public is poorly quantified, and little information on this subject is available in the medical literature. We surveyed 12 recent issues of popular health and bodybuilding magazines (1) to quantify the number of advertisements for food supplements, the number of products advertised, and the number and type of ingredients in these products; (2) to identify the purported health benefits of these products; and (3) as a preliminary effort to identify areas for future research. We counted 89 brands, 311 products, and 235 unique ingredients, the most frequent of which were unspecified amino acids; the most frequently promoted health benefit was muscle growth. We also found many unusual or unidentifiable ingredients, and 22.2% of the products had no ingredients listed in their advertisements. Health professionals may not be aware of how popular food supplements are or of a particular supplement's potential effects or side effects. In addition, patients may be reluctant to discuss their use of these products with traditional medical practitioners. We recommend that routine history taking include specific questions about patients' use of food supplements and that any possible adverse effects or side effects be reported to public health authorities.

Advertising↗
PubMed1992

Eosinophilia-myalgia syndrome in L-tryptophan-exposed patients.

OBJECTIVES: To study the incidence of eosinophilia-myalgia syndrome, the risk factors associated with the syndrome, and the clinical spectrum of illness associated with L-tryptophan use in an exposed population. DESIGN: Retrospective cohort and nested case-control studies of risk factors for eosinophilia-myalgia syndrome using inpatient and outpatient chart reviews, telephone interviews, and in-person patient interviews. Descriptive study of clinical course of L-tryptophan users. SETTING: Office practice of one psychiatrist based in a small city (population 43,467) in South Carolina. PATIENTS: Eligible subjects were all patients from the practice who used L-tryptophan during the 1989 study interval. Of these, 418 (87%) were interviewed. MAIN OUTCOME MEASURES: Clinical spectrum of illness associated with L-tryptophan use, including definite and possible cases of eosinophilia-myalgia syndrome. RESULTS: Among the 418 interviewed L-tryptophan users, we identified 47 definite cases (11%) and 68 possible cases (16%) of eosinophilia-myalgia syndrome, most of which involved patients who were using one retail brand of L-tryptophan (brand A). Among the 157 brand A users, we identified 45 definite cases (29%) and 36 possible cases (23%) of eosinophilia-myalgia syndrome, and the risk for the syndrome increased as the brand A dose increased. Fifty percent (19 of 38) of those using more than 4000 mg/day developed definite eosinophilia-myalgia syndrome, and 84% (32 of 38) developed either definite or possible eosinophilia-myalgia syndrome. On multivariate analysis, risk for definite eosinophilia-myalgia syndrome was associated with brand A dose and age of the patient; however, gender, race, and use of other medications were not associated with the syndrome. CONCLUSIONS: These results suggest that many people exposed to the agent causing eosinophilia-myalgia syndrome may develop illness, and dose of presumably contaminated L-tryptophan is the single most important predictor of eosinophilia-myalgia syndrome. The broad range of signs and symptoms reported by patients using L-tryptophan illustrates that a strict case definition may identify only about half of those affected.

Adult↗
PubMed1991

Long-term prognosis of extensive polyunit cantilevered fixed partial dentures.

The aim of this retrospective study was to elucidate the long-term prognoses of extensive fixed partial dentures including unilateral or bilateral polyunit cantilevers in patients with healthy but reduced periodontal support. Following periodontal therapy 36 cross-arch fixed partial dentures with two or more cantilever units unilaterally or bilaterally were fitted in 34 patients. In the prosthodontic design, special attention was given to the retention to long parallel preparations, to the dimensions of the framework, and to the occlusal design. After completion of therapy, the patients were enrolled in a regular maintenance care program and followed up for a period of 5 to 12 years. During this follow-up period one abutment tooth was fractured in one patient. One fixed partial denture with extremely reduced periodontal support was lost as a result of complete periodontal breakdown from occlusal trauma. For 33 fixed partial dentures, neither periodontal nor technical complications occurred.

Dental Abutments↗
PubMed1991

cis Acting RNA sequences control the gag-pol translation readthrough in murine leukemia virus.

The pol gene of the Moloney murine leukemia virus (M-MuLV) is expressed as a Gag-Pol fusion protein through an in-frame suppression of the UAG termination codon located between the two genes. The role of nucleotide context in suppression was investigated, in a rabbit reticulocyte lysate translation system, using site-directed mutagenesis. The results indicate that the translational readthrough is mediated by at least 50 bases long RNA sequence located 3' to the gag UAG termination codon. Within this sequence a short purine-rich sequence adjacent to the amber codon, highly conserved among different retroviruses, appears essential for M-MuLV suppression. Two alternative putative stem and loop like RNA structures can be drawn at the gag-pol junction, one abutting the gag UAG codon, and the second downstream to it. None of these structures appears to be important to the suppression process.

Animals↗