Delayed bupropion cardiotoxicity associated with elevated serum concentrations of bupropion but not hydroxybupropion.

CONTEXT: Bupropion overdose commonly causes generalized seizures and central nervous system depression. Less commonly, cardiotoxicity has been reported. The toxicity of the parent drug compared to its active metabolite hydroxybupropion is uncertain. CASE DETAILS: A 31-year-old man presented to the emergency department with altered mental status after an intentional overdose of bupropion. Three hours after admission he developed status epilepticus requiring intubation, and 13 h after admission he developed marked widening of the QRS complex and prolongation of the QTc interval. Serial serum bupropion levels peaked with the onset of cardiotoxicity (334 ng/mL) and fell into the therapeutic range within 24 h, which coincided with normalization of his ECG intervals. Levels of the metabolite hydroxybupropion peaked later (4302 ng/mL) and remained elevated even after neurological and cardiotoxic symptoms resolved. DISCUSSION: Cardiotoxicity appears to be caused primarily by bupropion rather than its active metabolite hydroxybupropion.

Metformin overdose-induced hypoglycemia in the absence of other antidiabetic drugs.

CONTEXT: Lactic acidosis is a well-recognized consequence of metformin. Hypoglycemia has been reported previously in metformin overdose, but the presence of other co-ingestions (e.g., a sulfonylurea) was not definitively excluded. CASE DETAILS: A 15-year-old girl ingested 75 g of metformin and 3 g of quetiapine. On examination in the emergency department 2 h later, she was drowsy but had normal vital signs. She developed lactic acidosis, hypotension, and recurrent and severe hypoglycemia (15 mg/dL and 20 mg/dL), requiring boluses of 50%dextrose. The first episode of hypoglycemia occurred approximately 4 h after ingestion. Serum metformin level 2 h after ingestion was 267 mg/L (therapeutic range, 0.465-2.5), and serum insulin was 2 mU/L (normal range, 6-35). Extensive laboratory investigation using high-resolution mass-spectrometry ruled out other possible hypoglycemic agents. She recovered after hemodialysis. DISCUSSION: Metformin overdose can cause severe hypoglycemia in the absence of other antidiabetic drugs. Potential mechanisms of metformin-induced hypoglycemia include decreased hepatic glucose production, decreased glucose absorption, and poor oral intake.

Identification of proteins from Escherichia coli using two-dimensional semi-preparative electrophoresis and mass spectrometry.

Escherichia coli is a gram-negative bacterium that causes sepsis and infections of the nervous system, and the digestive and urinary tracts. The availability of the complete nucleotide sequence encoding the E. coli K-12 genome has made this organism an excellent model for proteomic studies. Semi-preparative two-dimensional electrophoresis, including liquid phase isoelectric focusing (IEF), one-dimensional sodium dodecyl sulfate (SDS) polyacrylamide gel electrophoresis (PAGE) and gel elution, have for the first time been used in combination with matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry (MALDI-TOFMS), electrospray tandem mass spectrometry and database searching for rapid separation of proteins from a uropathogenic strain of E. coli. The identity of 30 proteins, including the membrane protein nmpC, was obtained using this approach.

Suitability of the lang II random dot stereotest for detecting manifest strabismus in 3-year-old children at child health centres in Sweden.

The aim of the study is to examine the suitability of the Lang II Random Dot Stereotest for use by district nurses in primary healthcare centres. The Lang Stereotest is an inexpensive method. It is easy to apply, but the child's co-operation is required. Approximately 100 district nurses were given detailed information and instruction by an orthoptist prior to a randomized population-based community trial initiated in 1993. In the county of Uppsala in Sweden, all 4293 children born in 1990 were randomized to one of the following four study groups: intervention, control, reliability or validity. All children were followed from birth to 6.5 y of age with respect to the occurrence of strabismus. The kappa statistic for test-retest reliability among district nurses was 0.65 (95% CI, 0.51-0.80). A validation of the outcomes of district nurses' against orthoptists' examinations using the Lang Stereotest showed a sensitivity of 0.33 (95% CI, 0.09-0.65) and a specificity of 0.85 (0.80-0.89). Of 113 cases of strabismus, 53% were detected within the first 3 y of life. Examination of 1132 3-y-old children using the Lang Stereotest enabled the district nurses to detect 11 new cases of strabismus. Only one of these cases was referred to an orthoptist as a direct consequence of the screening. The Lang Stereotest showed low reliability and low validity in this community trial. It is concluded that the Lang II Random Dot Stereotest is not suitable for the screening of manifest strabismus in unselected populations of 3-y-old children in Sweden, where a large proportion of cases of strabismus is detected during the first 3 y of life.

Ocular manifestations of incontinentia pigmenti.

PURPOSE: The study aimed to evaluate the ocular manifestations in patients with incontinentia pigmenti (IP). METHODS: Thirty patients from different parts of Sweden participated. Orthoptic and ocular examinations were performed as well as evaluation of refraction and visual acuity. RESULTS: Ocular manifestations, probably associated with IP, were found in 77% (23/30) of the patients. Thirteen had serious or vision-threatening eye manifestations in one eye, of whom 7 were totally blind in that eye from retinal detachments. Ten patients had minor retinal and/or corneal changes. CONCLUSION: Ocular lesions in patients with IP may be serious and lead to blindness because of retinal disease. Ophthalmological follow-up is essential in the neonatal period and such a programme is recommended.

Ethylene oxide sterilization impairs allograft incorporation in a conduction chamber.

Bone allograft processing often includes treatment with hydrogen peroxide for protein denaturation and sterilization by irradiation or ethylene oxide. The effect of these treatments on the osteoconductive properties of the graft was tested by measuring the new bone ingrowth distance into processed cancellous bone grafts in rats. Forty graft pairs were taken from rat tibias, and were frozen, defatted in chloroform-methanol, and dried. In addition, 1 graft of each pair was treated with 2% hydrogen peroxide, 2.5 Mrad irradiation, or by a Steri-Vac hospital ethylene oxide chamber. The grafts were placed in bone conduction chambers and implanted in rat tibias. Six weeks after implantation, the chambers were emptied, and the new bone ingrowth distance and scintimetric activity were measured. Ethylene oxide treatment impaired the new bone ingrowth distance by 68% and reduced the scintimetric activity by 51%. Another 10 defatted grafts, which had been ethylene oxide treated together with the grafts for implantation, were analyzed for levels of residual ethylene oxide, ethylene chlorohydrin, and ethylene glycol. All the measured residuals were below the detection limit of 20 parts per million, which was below the level recommended by the United States Food and Drug Administration. Ethylene oxide sterilization was more deleterious for bone allografts than expected.

Lipid extracted bank bone. Bone conductive and mechanical properties.

Lipid extraction by chloroform methanol previously has been found to increase the incorporation of frozen bone allografts. This effect may be because of a decreased immunologic response. In the present study, the ingrowth capacity into a grafted bone defect was investigated by using the bone harvest chamber model in rabbits. In a series of experiments, defatted and frozen allografts were compared at 1, 2, and 3 weeks; defatted allografts and defatted autografts were compared at 3 weeks; and frozen or defatted allografts and nongrafted defects were compared at 3 weeks. Evaluation was performed through histology, histomorphometry, and 99mTc-MDP scintimetry. The incorporation was better with defatted grafts: by histology at 1 week, mesenchymal tissue filled the intertrabecular space in defatted specimens and new bone formation started to occur. In contrast, frozen specimens showed a central soft tissue necrosis surrounded by inflammatory cells. Histomorphometry showed more new bone and more graft resorption in defatted allografts. At 2 and 3 weeks, there was no significant difference in new bone area, but at 3 weeks the scintimetric activity was higher in defatted allografts, probably caused by an increased remodeling rate. Since defatting did not cause increased scintimetric activity in previous autograft studies, these findings could indicate that there is a detrimental immunologic influence on frozen allografts. There were no differences between defatted autografts and allografts. In a second experiment, the biomechanical properties of defatted bone were investigated with a compression test on defatted and frozen bone cylinders taken from the calf femoral neck. No difference in biomechanical properties was found. It was concluded that lipid extraction produced a graft that was better incorporated than a nondefatted graft, with no loss of mechanical function.

Increased bone ingrowth distance into lipid-extracted bank bone at 6 weeks. A titanium chamber study in allogeneic and syngeneic rats.

In previous rabbit chamber experiments, lipid extraction has been shown to increase bank bone incorporation, as measured by scintimetric activity at 3 weeks. In the present study, the new bone ingrowth distance was measured by histomorphometry at 6 weeks using a titanium chamber model in rats. By insertion into bilateral bone conduction chambers, frozen grafts were compared with grafts that had been processed by lipid extraction. To evaluate the effects of lipid extraction further, the group of 26 rats was divided into three subgroups according to MHC haplotype, namely a heterogeneous group (outbred Sprague-Dawley rats), a mismatched group, and a syngeneic group. In the total material, defatted grafts showed a 58% greater new bone ingrowth distance and a 31% higher scintimetric activity over controls. The effect of defatting was not shown to be due to immunologic factors. In general, rats with a lower capacity to incorporate bone grafts showed a larger positive effect of defatting.

Comparison of talonavicular dowel arthrodesis utilizing autogenous bone versus defatted bank bone.

A simple dowel arthrodesis of the talonavicular joint in an early stage of destruction can reduce pain and prevent the development of valgus deformity in the rheumatoid hindfoot. Previously, we used autogenous dowels made from the iliac crest. In order to facilitate the operation and to get a better fitting dowel, we tried defatted cancellous allograft dowels from which marrow tissue had been removed. The dowels were prepared from femoral heads in our surgical bone bank. At operation, the dowels were embedded in fresh marrow aspirate from the iliac crest and the arthrodeses were stabilized with a staple. Results were evaluated by clinical examination and radiography. The results of four patients were compared with an earlier study of eight patients using autogenous dowels taken from the iliac crest. With both techniques, the patients were relieved of pain in the talonavicular joint, but some had pain from other hindfoot joints. With autogenous dowels, all eight patients healed with radiographic bony union, but with allogenous dowels, the four patients developed fibrotic nonunion. The results indicate that talonavicular arthrodesis should be made using only autologous dowels.

Lipid extraction decreases the specific immunologic response to bone allografts in rabbits.

The immunologic response against frozen bank bone is generally considered to have no clinical importance. In a previous study, the bone formation rate in frozen allografts was measured at standardized conditions in the Bone Harvest Chamber. By defatting frozen allografts, the bone formation rate increased. In the present study, the effect of defatting was further investigated, as the specific immunologic influence was excluded by using autografts. Pairs of grafts were frozen and one graft in each pair was defatted with chloroform/methanol. With these autografts there was no difference in bone formation rate between defatted and non-defatted implants, measured with 99mTc-MDP. Combined with the previous experiments, the results indicate that the increased bone formation rate in defatted allografts is caused by the removal of specific cell surface antigens. Thus, the immunologic reaction to bank bone can be diminished by defatting.

Effects of basic fibroblast growth factor on bone allografts. A study using bone harvest chambers in rabbits.

Bone grafts which have been supplemented with a growth factor might incorporate faster. In this study we investigated the effect of basic fibroblast growth factor (bFGF). Titanium bone harvest chambers were implanted bilaterally in the proximal tibia of rabbits. These chambers were pierced by a transverse bone ingrowth canal from which 1 x 1 x 5 mm cancellous bone rods were repeatedly harvested at 5 weeks intervals. The bone rods to be used as allografts were frozen as ordinary bank bone, and then lipid-extracted. This treatment yields a graft which elicits less of an immunologic response than allografts which are only frozen and thawed. Before implantation, the bone rods were soaked in a cellulose gel containing 0.5 microgram/ml recombinant human bFGF or gel without bFGF as a control. The grafts were then implanted pair wise (bFGF and control) in the chambers of recipient rabbits. These chambers were harvested after 2 weeks. Evaluation was made by Tc-MDP scintimetry, histomorphometry and histology. Upon histology new living tissue had filled the grafted chambers entirely and partly replaced the graft. bFGF induced an increased amount of pre-osteoblastic tissue in the bFGF-treated grafts (p < 0.02), but there was no difference in the amount of osteoid or new bone.

Mortality pattern among pulp and paper mill workers in Sweden: a case-referent study.

The mortality pattern among Swedish pulp and paper mill workers was evaluated in a case-referent study encompassing 4,070 men decreased during the period 1950-1987. The subjects were identified from the register of deaths and burials in six parishes. A significantly increased mortality was seen for diabetes mellitus and for secondary tumors of the lung and liver among the pulp and paper mill workers. Indications of excess risks were also found for obstructive lung disorders, pulmonary emboli, accidents, and pneumonia, as well as for malignant lymphomas, leukemias, and cancer of the pancreas and stomach. In the only parish where a sulfite process was exclusively used, cancer of the digestive tract and especially of the rectum was found to be in excess. Except for this parish, the sulfate process predominated in the plants included. The mortality pattern found in this study is in reasonable agreement with findings in various studies from this type of industry.

Lipid extraction enhances bank bone incorporation. An experiment in rabbits.

We implanted frozen allogeneic cancellous bone in rabbit skeletal defects and compared the bone-forming response with that from similar implants that had also been extracted with chloroform/methanol. The donor bone was harvested from a previously implanted titanium chamber that is spontaneously filled with reproducible amounts of cancellous bone. It was processed as frozen bank bone, then transferred to an identical, but empty, chamber in another rabbit. Extraction of lipids before implantation increased the ingrowth of new bone into the transferred bone, as measured by 45Ca and 99mTc-MDP activity. A simple treatment with fat solvents may reduce some of the drawbacks of ordinary bank bone.

Treatment of asymptomatic amebiasis in homosexual men. Clinical trials with metronidazole, tinidazole, and diloxanide furoate.

In a randomized trial, the authors treated 42 asymptomatic homosexual men who had Entamoeba histolytica in fecal specimens with either metronidazole or tinidazole (study 1). They treated both groups initially with 2,000 mg in a single dose, and in case of failure with 2,000 mg daily for 5 days. In cases of repeated failure, the authors prescribed a dosage of 500 mg of diloxanide furoate three times per day (TID) for 10 days. In a subsequent study (study 2) the authors treated 49 asymptomatic homosexual men who had E. histolytica in fecal specimens with 500 mg of diloxanide furoate TID for 10 days. In study 1, the parasitological cure rates (PCR) for metronidazole and tinidazole were 29%-56%. Among the men treated with diloxanide furoate, the PCR was 93%. In study 2 the PCR with diloxanide furoate was 88%, which was significantly better (P less than .05) than metronidazole/tinidazole treatment in study 1. The present studies show that diloxanide furoate is an effective treatment of amebiasis in asymptomatic patients.

Characterization of airborne dust in a soft paper mill.

The characteristics of airborne dust in a soft paper production plant have been characterized by scanning and transmission electron microscopy. A combination of X-ray diffraction, electron diffraction and energy-dispersive X-ray flouresence spectroscopy (EDX) was used to determine the structure and composition of the different components. Size distribution determination and phase identification were carried out. Besides the cellulose fibres, fibres of kaolinite, wollastonite, talc and other silicates were also identified. Gravimetric analysis and fibre counting by optical phase contrast microscopy were used to determine total dust and fibre concentrations. Total dust exposure at the plant was generally below 3 mg m-3. The respirable fraction of the total dust concentrations varied from 15 to 70%. The inorganic dust was 36 +/- 15% of the total dust. The ratio of inorganic fibres to total fibre concentration at the plant varied between 10 and 15%.

Mortality from asthma and chronic obstructive pulmonary disease among workers in a soft paper mill: a case-referent study.

In a case-referent study encompassing 33 cases and 228 referents the potential risk for asthma and chronic obstructive pulmonary disease and respiratory cancer among workers in a soft paper mill was evaluated. The cases were selected from registers of deaths and burials in the parishes around the paper mill. Information on exposure was obtained from the personnel register of the mill but because of shortage of information the cases could only be classified as "exposed" or "non-exposed." At some places in the mill the concentrations of paper dust had previously been high, 10-30 mg/m3. Employment at the paper mill was found to be associated with an increased risk of bronchial asthma and chronic obstructive pulmonary disease (odds ratio = 3.8, p less than 0.05).

Lung function and respiratory symptoms among workers in a soft paper mill.

The aim of the present cross-sectional study was to investigate whether long-term exposure to soft paper dust causes impairment of lung function. Exposed workers (n = 287) and referents (n = 79) were investigated, using spirometry and questionnaires. Personal samplings of total dust showed that the actual mean concentrations did not exceed 3 mg/m3. The exposed subjects were divided into three categories according to historical and present exposure to paper dust; low exposure, moderate exposure and high exposure. The study did not show any lung function impairment due to exposure to paper dust. However, the exposed subjects had a significantly increased prevalence of symptoms from both the upper and lower airways as well as an increased prevalence of reported asthma. On the basis of our study, we conclude that lung function impairment does not occur among workers exposed to mean levels of soft paper dust below 5 mg/m3.

Lung function in workers exposed to soft paper dust.

In a cross-sectional study, 13 nonsmoking men with heavy exposure to paper dust were compared with 14 unexposed men, mainly office workers, employed at the same paper mill. They were studied using questionnaires, physical examinations, pulmonary function studies, and chest radiographs. Among those exposed there was an increased lung elastic recoil pressure (Pel) compared with controls which was significant (p less than 0.05) at the maximal level of total lung capacity (100% TLC). Furthermore, among the exposed workers there was also a significantly (p less than 0.05) decreased residual volume (RV). Two of the exposed men underwent lung biopsies, one of which showed fibrotic alveolar walls. Among the exposed there was also a significant (p less than 0.05) predominance of symptoms from the lower respiratory tract. We suggest that the observed pulmonary function impairment taken together with the histological examination of the lung biopsies are signs of a nonspecific reaction to high levels of paper dust.