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Biomedical subjects

S M Hou

Publications and source records attributed to S M Hou.

At least 55 records · Page 3Linked to original sources

Wrist arthrodesis using a slab bone graft from the dorsal radius.

Arthrodesis is a well-established procedure for the management of wrist deformity, instability, and arthritis resulting from various causes. Several techniques, with or without internal fixation or heterotopic bone grafting, have been described, but no single procedure has gained general acceptance. We present our results using a simple and reliable technique that employs a local bone graft and light internal fixation. From 1987 to 1996, eight consecutive patients with wrist lesions were treated using a modified Gill procedure for arthrodesis. The average age of patients was 62 years and the mean follow-up period was 4 years. A slab corticocancellous bone graft harvested from the dorsal aspect of the distal radius was turned about to cover the fusion mass from the distal radius to the third metacarpal bone. Kirschner wires and tension band wires were used to fix the wrist and compress the bone graft. A long arm cast was applied for 6 weeks, followed by a short arm cast until arthrodesis was achieved. The wrist position was well maintained by the tension band wire alone thereafter. Pain relief, grip strength, and assessment of daily activities were documented. Solid fusion was achieved smoothly in all cases and all patients were satisfied with the results. We recommend this simple and reliable technique for wrist arthrodesis.

Aged↗

Biomechanical comparison of antegrade and retrograde nailing of humeral shaft fracture.

A pair-controlled study was conducted to compare biomechanical properties of antegrade and retrograde nailing of humeral fractures. First, six paired fresh anatomic specimen humeri were used to compare the properties of humeri fractured at the middle to distal diaphyses junction that were nailed from the retrograde approach with the Humeral Locked nail with those of contralateral intact humeri. An 18 additional pairs were divided into three equal groups by distal, proximal, or mid-diaphysis location of a standardized 5-mm bone defect to simulate unstable fractures. The retrograde and antegrade nailings were performed in each pair in a random manner. Nail and bone constructs were tested for bending stiffness by nondestructive three-point bending and for torsional stiffness by destructive torsional tests. Compared with intact humeri, fractured humeri fixed with nails had 28.6% posteroanterior and 31.4% mediolateral bending stiffness, 22.5% torsional stiffness, and 43.3% failure torque. For distal fractures, retrograde nailing showed significantly more initial stability and higher bending and torsional stiffness; for proximal fractures, antegrade nailing showed similar properties. For middle to distal diaphyses junction fractures, retrograde and antegrade nailing were indistinguishable. The defect created as an entry portal for retrograde nailing reduced the bone strength only 11.1%. These results suggest that retrograde nailing, which is less detrimental to shoulder function than is antegrade nailing, is an acceptable alternative treatment for humeral shaft fractures. In addition, nailing from the short to the long bone segments can improve mechanical properties of the fixation construct because of better nail and bone interface purchase.

Biomechanical Phenomena↗

Splicing mutations at the HPRT locus in human T-lymphocytes in vivo.

We studied 58 splicing mutations originating in vivo at the hypoxanthine guanine phosphoribosyltransferase (HPRT) locus in T-cells of 30 nonsmoking males. A nonrandom distribution of skipped exons was seen after cDNA sequence analysis, with 71% involving exons 2-3 (15), 4 (11), and 8 (15). The mutations likely to have caused the aberrant splicing were identified in 36 mutants by genomic sequencing. The most frequently observed mutations were simple base substitutions (27) and small deletions (7). Among the base substitutions, 23 occurred in the splice consensus sequences, mainly at the highly conserved dinucleotides (21), and preferentially in the acceptor sites (15). The remaining four base substitutions occurred in the coding sequence where one tandem base substitution, one single bp insertion, and two single bp deletions were also observed. The predicted change in three of the base substitutions would be a stop codon. The tandem mutation (CC --> TT) occurred at position 550-551, a possible hotspot for splicing mutations (five of nine previously reported base substitutions at position 551, all C --> T, resulted in abnormal splicing). Four of the base substitutions were new HPRT mutations, two in splice sites (IVS7-3T --> G and IVS8 + 3A --> C) and two in the coding sequence (307A --> T and 594C --> G). All the small deletions (> 1 bp) affected the acceptor sites. The only three identified mutations related to skipping of exons 2 and 3 were located within exon 3, suggesting a frequent involvement of unknown splicing elements distant from these exons.

Base Sequence↗

Glutathione S-transferase mu1 and N-acetyltransferase 2 genetic polymorphisms and exposure to tobacco smoke in nonsmoking and smoking lung cancer patients and population controls.

We conducted a case-control study to assess the risk of lung cancer in relation to genetic polymorphisms of the detoxifying enzymes glutathione-S-transferase mu1 (GSTM1) and N-acetyl transferase 2 (NAT2), focusing on never-smokers, women, and older people. The study base consisted of persons > or =30 years of age in Stockholm County from 1992 to 1995. We recruited never-smoking lung cancer cases and a sex- and age-matched sample of ever-smoking cases at the three county hospitals mainly responsible for diagnosing and treating lung cancer. A total of 185 cases (25.4% men; 47.6% never-smokers) and 164 frequency-matched population controls (28.7% men; 48.2% never-smokers) supplied blood for genotyping. Detailed information was collected by interview on active and passive smoking, occupations, residences, and diet. The overall odds ratio (OR) for lung cancer associated with the GSTM1 null (GSTM1-) versus GSTM1+ genotype was 0.8 [95% confidence interval (CI), 0.5-1.2], with an OR close to unity among smokers, and lower ORs suggested among never-smokers. For NAT2 slow versus rapid acetylator genotypes, the OR was 1.0 (95% CI, 0.6-1.5) overall, which broke down into an increased risk for slow acetylators among never-smokers but an increased risk for rapid acetylators among smokers. Among never-smokers, a gene interaction was suggested, with combined slow acetylator and GSTM1+ genotype conferring particularly high risk (OR = 3.1; 95% CI, 1.1-8.6), but no clear pattern emerged among smokers. A detailed analysis among smokers showed no interaction between pack-years of smoking and the GSTM1 genotype but suggested a steeper increase in risk with increasing pack-years of smoking exposure for rapid than for slow acetylators. Our results do not support a major role for the GSTM1 genetic polymorphism as a risk factor for lung cancer among smokers or nonsmokers. There was, however, some suggestion that the slow acetylator genotype may confer an increased risk among never-smokers and that the rapid acetylator genotype interacts with pack-year dose to produce a steeper risk gradient among smokers.

Acetylation↗

Combination leflunomide and cyclosporine prevents rejection of functional whole limb allografts in the rat.

Whole rear limbs were transplanted from Brown Norway or Lewis rat donors to Lewis rat recipients (n=6 per group). One group of allograft recipients was treated with leflunomide (10 mg/kg/24 hr/orally) and cyclosporine (5 mg/kg24 hr/orally) starting 2 days before to surgery. Treatment continued for 60 days or until graft rejection. Untreated allografts were rejected over 6-8 days. After isograft transplantation, weight bearing began by day 17-25 after surgery. Sensory function was restored by 50 days after surgery. All allografts in the drug-treated group survived the 60-day period; survival in this group was significantly longer (P=0.0001) than the untreated controls. Weight bearing began by day 30, but was incomplete in two rats at 60 days. Peroneal nerve function was present in half the rats at 60 days after surgery. Leflunomide combined with cyclosporine prevented whole limb allograft rejection across a major histocompatibility barrier.

Animals↗

Comparison of systemic absorption of aqueous and liposomal lidocaine following intra-articular injection in rabbits.

Aqueous lidocaine is a local anesthetic that is frequently used in intra-articular injection. However, aqueous lidocaine may be less than ideal because of its rapid absorption. Liposomes can serve as drug carriers for encapsulating lidocaine. Both aqueous lidocaine and liposomal lidocaine were injected into knee joints of adult rabbits and the pharmacokinetic changes were studied. The peak serum level of lidocaine from the liposomal preparation was significantly lower than that from the aqueous preparation. The amount of lidocaine absorbed in 4 hours was also significantly lower in the liposomal group. This phenomenon may have been due to local accumulation of liposomal lidocaine and the slow release of lidocaine from liposomes. Intra-articular use of liposomal lidocaine may have advantages over the aqueous form because of its lower systemic serum concentration.

Absorption↗

Treatment of humeral shaft fractures by retrograde locked nailing.

From 1992 to 1994, 29 middle and 19 distal humeral shaft fractures (39 acute fractures, six nonunions, and three pathologic fractures) in 48 patients were treated by retrograde locked nailing. The first eight acute fractures were treated with Seidel nails, the other 40 fractures with specially designed humeral locked nails. Nails were inserted from the supracondylar (6) or the olecranon fossa (42) entry portal. With a single operation, all acute fractures and nonunions achieved osseous union without serious complications. The average time to union was 8.2 weeks for acute fractures and 14.2 weeks for nonunions. Recovery of shoulder function was complete. Elbow motion was excellent in all but one nonunion that resulted from a Type IIIB open fracture. Two patients with supracondylar entry had apex to posterior angular malunion. One patient with a distal comminuted fracture had varus malunion. Three patients had an iatrogenic bony split, but healing was unaffected. Patients with pathologic fractures maintained satisfactory arm function postoperatively. Given the few complications and good functional recovery seen in this study, retrograde locked nailing appears to be a good alternative treatment in middle and distal humeral shaft fractures. The olecranon fossa approach, with more linearity to the humerus, is preferred. In the authors' experience, humeral locked nails are inserted more easily and are associated with fewer complications than are Seidel nails.

Adolescent↗

Laparoscopic management of ruptured pyogenic liver abscess.

Intraperitoneal rupture of pyogenic liver abscess is a rare but potentially fatal disease, often involving the elderly, who are commonly of poor surgical risk with background of significant medical illness. Accurate preoperative diagnosis is difficult and often necessitates exploratory laparotomy for peritonitis. We report a case of ruptured cryptogenic solitary liver abscess presented with acute peritonitis that was successfully treated laparoscopically. The laparoscopic approach obviated the access trauma, confirmed the diagnosis, was able to drain the abscess, as well as provided microbiology and histology samples. A thorough peritoneal lavage could be also performed. The use of laparoscopic ultrasound could also localize concomitant abscesses and detect associated biliary tract pathology.

Aged↗

Magnetic resonance imaging of glomus tumour in the hand.

Glomus tumours of the hand are benign tumours that arise from the neuromyoarterial apparatus. The most common site for a glomus tumour is in the distal phalanx. They frequently display a classic triad of symptoms-pain, tenderness and temperature sensitivity. Ten treated cases examined with magnetic resonance imaging (MRI) preoperatively are described. All were female with a mean age of 43 years. All except 2 suffered the classic triad of symptoms. The mean duration from onset of symptoms to therapeutic intervention was 7.4 years. MRI depicted the tumours in excellent detail and aided diagnosis in the 4 patients without subungual blue discolouration. The lesions showed a low signal on the T1-weighted image and a high signal on the T2-weighted image. All except 3 were located in the subungual region. All patients underwent surgical excision with pathological confirmation. The postoperative course was smooth and there were no sequelae. High resolution MRI, providing a clear contrast between tumorous and normal tissues, has proved to be a useful non-invasive method for imaging glomus tumours in the hand.

Adolescent↗

GSTM1 and NAT2 genotypes and urinary mutagens in coke oven workers.

The influence of the metabolic genotypes GSTM1 and NAT2 on the urinary excretion of mutagens in 46 coke oven workers (27 of them smokers) was studied. Exposure to polycyclic aromatic hydrocarbons (PAH) was estimated from urinary 1-pyrenol levels, which varied from 0.23 to 5.59 micromol/mol creatinine. Fourteen urine samples (30.4%), all but one belonging to smokers, were positive for mutagenic activity (i.e. at least one of the assayed doses was able to double the number of spontaneous revertants). Nine of the urine-positive subjects were both GSTM1-null and NAT2-ss (64.3%), while the same combination of genotypes was found in nine out of 31 urine-negative subjects (29.0%) (P < 0.05). Significantly more smoking workers with the genotype combination GSTM1-null/NAT2-ss showed positive urine mutagenicity than the other subjects (75.0 versus 28.6%, P < 0.05). Smokers with the slow acetylator genotype showed a significantly higher frequency of positive urine samples than smoking fast acetylators (64.7 versus 22.2%, P < 0.05). Our results suggest that smoking coke oven workers with genotypes unfavourable for detoxification of aromatic amines (NAT2-ss) and PAH (GSTM1-null) may have an increased risk of developing bladder cancer.

Arylamine N-Acetyltransferase↗

Sequence analysis of deletion mutations at the HPRT locus of human T-lymphocytes: association of a palindromic structure with a breakpoint cluster in exon 2.

To study the structure and mechanism of deletion mutation in human somatic cells in vivo, we have identified and sequenced the breakpoints of 16 independent deletions at the hypoxanthine-guanine phosphoribosyl transferase (HPRT) locus in human T-lymphocytes. Seven deletions were found in exon 2, three in each of exon 3 and 6, and one in each of intron 3, exon 8 and exon 9. Most of the deletions seemed to result from non-homologous recombination, possibly by a slippage-misalignment mechanism between short repeat sequences. Putative secondary DNA structures, possibly acting as intermediates in the deletion formation, were identified in several mutants. Six of the seven exon 2 deletions had a breakpoint within a 12 bp region (in the 5' end of exon 2) which contains a 9 nucleotide palindrome (AACCAGGTT) and is preceded by a TGA direct repeat tract. One of the mutants had two deletions in tandem, separated by the palindrome. Another mutant, in which 23 bp containing the palindromic sequence was deleted, had an additional base (C) inserted between the breakpoints forming a direct repeat (gACGAC) in the deletion junction. Taken together with previously reported deletion mutations at the HPRT locus, these results suggest that the deletion cluster in the 5' part of HPRT exon 2 in T-cells in vivo is promoted by the 9 nucleotide palindrome sequence and the TGA repeat tract. The former may act as a stabilizer in a putative intermediate structure, and the latter may induce slippage and misalignment during replication.

Base Sequence↗

Ultrastructural studies on myofibrillogenesis and neogenesis of skeletal muscles after prolonged traction in rabbits.

Little is known about the morphological response of muscle after long term traction. The purpose of this study was to investigate the morphological changes of skeletal muscle during limb lengthening. After application of mini-extraskeletal fixator, the hindlimb of New Zealand white rabbit was osteotomized and then slowly lengthened at the rate of 1 mm/day up to a 20 mm gain in length. The muscles of hindlimbs were perfused and dissected. Morphological studies were performed at electron microscopic level. Transmission electron microscopy revealed foci of microtrauma at the myotendinous junction. The distance between the muscle fibers and tendon parenchyma increased, with numerous primitive mesenchyme-like cells interposed within this gap. The cytoplasmic space of these cells was devoid of myofibril formation at the ends of stretched fibers. Within the satellite near the myotendinous junction myofilament production was observed in various gradations of maturation. It is concluded that myofibrillogenesis with traction neogenesis of skeletal muscle during limb lengthening does exist and occurs mainly near the myotendinous junction. The myotendinous junction in mature skeletal muscle actively participated in the process of limb lengthening.

Animals↗

Latissimus dorsi free flap in orthopedic reconstructive surgery.

In complex musculoskeletal diseases, soft-tissue reconstruction is usually the key to a good clinical result. Selection of an ideal flap is a critical step in successful reconstruction. We performed latissimus dorsi free flap transfers in 52 patients with orthopedic disorders from 1988 to 1993. Recipient sites were the lower extremities (44), upper extremities (six) and buttocks (two). The indications for flap surgery comprised chronic ulcer (seven), osteomyelitis (nine), compound fractures (28), crushing or avulsion injuries (six) and malignancy (two). All of the flaps survived and the therapeutic goals were satisfactorily achieved. One patient had revision of vascular anastomosis and five patients underwent skin regrafting. Of eight patients who complained of bulkiness of the flap, only two patients had debulking surgery. No chronic infection occurred in either skeletal or soft tissue after flap coverage in any patients. Two of five heel flaps had initial ulcers and became endurable after one year. Two patients with malignancy were treated with wide resection and coverage with the flap. The esthetic and functional morbidity of the donor site was minimal. Through several modifications--segmentalization, tailoring, thinning and multiple islanding--the flaps become so versatile that they can be applied to different kinds of tissue defects in different locations of the body. This series of patients revealed the flap to be the most useful armament in the reconstruction of complex musculoskeletal diseases, particularly for orthopedic microsurgeons.

Adolescent↗

Hprt mutant frequency and GSTM1 genotype in non-smoking healthy individuals.

The T-cell cloning assay which combines mitogen- and growth factor-dependent expansion of lymphocyte clones with thioguanine selection of hypoxanthine-guanine phosphoribosyl transferase (hprt)-negative cells has been extensively used for studying human somatic gene mutation in vivo. However, large interindividual variations in the hprt mutant frequency (MF), much of which is not explained by donor attributes such as age and smoking habit, and interlaboratory variations in the experimental methodology, including cloning efficiency (CE), call for further developments of the cloning protocol and additional population studies. Using an improved T-cell cloning method, we have studied in vivo hprt MF of 76 non-smoking healthy males aged 23-77 years. The addition of 5% human serum to the growth medium was found to produce a consistently high CE of 61% in average. The MF, ranging from 1.4 to 22.6 x 10(-6) with a mean of 8.6 x 10(-6), increased significantly (P < 0.0001) with age, by 2% per year. A significant (P = 0.002) inverse relationship between MF and CE was observed. Using a PCR-based technique for GSTM1-genotyping, we also studied the relationship between MF and GSTM1 polymorphism. The 38 (50%) GSTM1-negative individuals showed a 20% higher mean MF than the 38 (50%) GSTM1-positive individuals. The difference was however not significant, neither before (P = 0.1) nor after (P = 0.5) correction for CE and the significantly (P = 0.04) higher mean age in the GSTM1-negative group. This study shows that age contributes more than GSTM1 polymorphism to the large interindividual variation in the hprt MF of non-smokers. The relationship between GSTM1 polymorphism and hprt MF in smokers remains to be investigated.

Adult↗

Methylglyoxal induces hprt mutation and DNA adducts in human T-lymphocytes in vitro.

Methylglyoxal (MG) is a mutagen present in several foodstuffs, including coffee. We have used the 32P-postlabelling method to measure MG-deoxyguanosine adduct levels, and the T-cell cloning technique, to study the frequency of hprt (hypoxanthine-guanine phosphoribosyl transferase) mutant cells after treatment of human lymphocytes with MG in vitro. The mutant induction by single (18 hr) high-dose (1.0-1.5 mM) treatment was comparable to that induced by repeated (3 x 48 hr) low-dose (0.1-0.4 mM) treatment. The latter also correlated with the adduct levels measured in the same experiment. The relative cell survival measured by direct cloning after the final treatment agreed well with the growth curves monitored during the expression phase. Our results show that MG is capable of inducing hprt mutations as well as DNA adducts in human lymphocytes at doses with low cytotoxicity. However, significant adduct formation (two- to threefold) could be obtained only after the first exposure in cells subjected to a repeated treatment protocol, and the induced mutant frequency was low (two- to fourfold over background). Thus, MG seems to be a comparatively weak mutagen in this system.

Adult↗

Analysis of mutation at the hprt locus in human T lymphocytes.

Studies of mutation at the hypoxanthine phosphoribosyl transferase (hrpt) locus in human T-cells have the potential to elucidate the molecular basis of in vivo mutagenesis, reveal exposure dependent changes in ther background frequency of mutation, and provide knowledge on individual sensitivity. Styrene exposed lamination workers in Bohemia showed a significantly higher frequency of hprt mutant cells than Swedish control populations studied simultaneously. In a study of 47 healthy, non-smoking male bus maintenance workers exposed to diesel exhausts, soot and oil, and 22 unexposed controls, a significant correlation (P = 0.008) was obtained between the levels of aromatic DNA adducts and frequencies of hprt-mutant T-cells. In the group of workers with the highest exposure, subjects with glutathione S-transferase (GSTM1) deficiency showed significantly higher (P < 0.05) frequency of hprt mutant T-cells than GSTM1-positive subjects. The highest adduct levels were found in subjects with the combined genotype of GSTM1 and NAT2 deficiency (GSTM1-negative slow acetylators). These results indicate that GSTM1 and NAT2 genotypes may play a role in determining the individual levels of hprt mutation and DNA adducts. Using PCR-based screening methods, hprt mutations have been classified in 462 T-cell clones from 43 subjects in this study population. Deletions were found in 3% of the mutants, coding errors in 81% and splice mutations in 17%. Transitions and transversions were equally common, and all types of base substitutions were detected.

Arylamine N-Acetyltransferase↗

DNA adducts caused by tamoxifen and toremifene in human microsomal system and lymphocytes in vitro.

DNA-binding of tamoxifen and toremifene was studied in rat in vivo, in human and rat microsomes in vitro, and in cultured primary human lymphocytes by 32P-postlabelling. Only tamoxifen caused DNA adducts in rat liver. Both compounds induced adducts in both rat and human microsomal systems and in cultured lymphocytes. The levels of adducts in microsomes and lymphocytes were low, ca. 1 adduct/10(9) nucleotides. Toremifene showed lower binding in each system, and in lymhocytes adducts were only detected at a cytotoxic dose level.

Animals↗