Investigation of induced recirculation during planned ventilation system maintenance.

The Office of Mine Safety and Health Research (OMSHR) investigated ways to increase mine airflow to underground metal/nonmetal (M/NM) mine working areas to improve miners' health and safety. One of those areas is controlled recirculation. Because the quantity of mine air often cannot be increased, reusing part of the ventilating air can be an effective alternative, if implemented properly, until the capacity of the present system is improved. The additional airflow can be used to provide effective dilution of contaminants and higher flow velocities in the underground mine environment. Most applications of controlled recirculation involve taking a portion of the return air and passing it back into the intake to increase the air volume delivered to the desired work areas. OMSHR investigated a Nevada gold mine where shaft rehabilitation was in progress and one of the two main fans was shut down to allow reduced air velocity for safe shaft work. Underground booster fan operating pressures were kept constant to maintain airflow to work areas, inducing controlled recirculation in one work zone. Investigation into system behavior and the effects of recirculation on the working area during times of reduced primary ventilation system airflow would provide additional information on implementation of controlled recirculation into the system and how these events affect M/NM ventilation systems. The National Institute for Occupational Safety and Health monitored the ventilation district when both main fans were operating and another scenario with one of the units turned off for maintenance. Airflow and contaminants were measured to determine the exposure effects of induced recirculation on miner health. Surveys showed that 19% controlled recirculation created no change in the overall district airflow distribution and a small reduction in district fresh air intake. Total dust levels increased only modestly and respirable dust levels were also low. Diesel particulate matter (DPM) levels showed a high increase in district intake mass flow, but minor increases in exposure levels related to the recirculation percentage. Utilization of DPM mass flow rates allows input into ventilation modeling programs to better understand and plan for ventilation changes and district recirculation effects on miners' health.

Identification and pharmacological characterization of the prostaglandin FP receptor and FP receptor variant complexes.

BACKGROUND AND PURPOSE: A prostamide analogue, bimatoprost, has been shown to be effective in reducing intraocular pressure, but its precise mechanism of action remains unclear. Hence, to elucidate the molecular mechanisms of this effect of bimatoprost, we focused on pharmacologically characterizing prostaglandin FP receptor (FP) and FP receptor variant (altFP) complexes. EXPERIMENTAL APPROACH: FP receptor mRNA variants were identified by reverse transcription-polymerase chain reaction. The FP-altFP4 heterodimers were established in HEK293/EBNA cells co-expressing FP and altFP4 receptor variants. A fluorometric imaging plate reader was used to study Ca2+ mobilization. Upregulation of cysteine-rich angiogenic protein 61 (Cyr61) mRNA was measured by Northern blot analysis, and phosphorylation of myosin light chain (MLC) by western analysis. KEY RESULTS: Six splicing variants of FP receptor mRNA were identified in human ocular tissues. Immunoprecipitation confirmed that the FP receptor is dimerized with altFP4 receptors in HEK293/EBNA cells co-expressing FP and altFP4 receptors. In the studies of the kinetic profile for Ca2+ mobilization, prostaglandin F2alpha (PGF2alpha) elicited a rapid increase in intracellular Ca2+ followed by a steady state phase. In contrast, bimatoprost elicited an immediate increase in intracellular Ca2+ followed by a second phase. The prostamide antagonist, AGN211335, selectively and dose-dependently inhibited the bimatoprost-initiated second phase of Ca2+ mobilization, Cyr61 mRNA upregulation and MLC phosphorylation, but did not block the action of PGF2alpha. CONCLUSION AND IMPLICATIONS: Bimatoprost lacks effects on the FP receptor but may interact with the FP-altFP receptor heterodimer to induce alterations in second messenger signalling. Hence, FP-altFP complexes may represent the underlying basis of bimatoprost pharmacology.

A study of logger fatalities from 1992-2000.

OBJECTIVES: To determine if certain loggers are at increased risk of death during logging operations. METHODS: Statistical analysis of 780 logger fatalities for a nine year period (1992-2000). RESULTS: The major findings are: (1) treefallers suffer nearly 63% of all fatalities, (2) the region where the fatality occurred and the size of the employer were not significant factors that contributed to a high percentage of treefaller fatalities, and (3) the Northeast and Midwest regions showed a higher percentage of fatalities compared with the South and West regions. CONCLUSIONS: Overall, the logger fatality rate for 1992-2000, compared with 1980-88 has decreased slightly; however, treefallers continue to be the group of loggers who suffer the highest fatality rate.

High tibial osteotomy with a calibrated osteotomy guide, rigid internal fixation, and early motion. Long-term follow-up.

BACKGROUND: We studied the results of sixty-four valgus-producing high tibial osteotomies performed with the use of a calibrated osteotomy cutting guide and rigid internal fixation, and followed by early motion, in fifty-six patients who had medial unicompartmental osteoarthritis and varus malalignment. Long-term studies have demonstrated that a high tibial osteotomy performed with staple fixation and followed by immobilization in a cast has an expected survival rate of approximately 85 percent at five years and 60 percent at ten years (in studies of ninety-five knees and 213 knees, respectively). To the best of our knowledge, there are no long-term reports on high tibial osteotomies performed with a calibrated osteotomy cutting guide and rigid internal fixation and followed by early motion. METHODS: The indications for high tibial osteotomy were medial unicompartmental osteoarthritis and varus malalignment. A lateral closing-wedge osteotomy was performed. The patients were reexamined to obtain a knee score, to make lateral radiographs of both knees, and to make a full-length anteroposterior radiograph (showing the entire lower extremity, including the hip and ankle) of the involved knee with the patient standing. RESULTS: Twenty-one knees were treated with a subsequent total knee arthroplasty at an average of sixty-five months after the high tibial osteotomy. The remaining forty-three knees had a good or excellent clinical result, with an average knee score of 94 points at an average of 8.5 years after the osteotomy. Survivorship analysis showed an expected rate of survival, with conversion to a total knee arthroplasty as the end point, of 85 percent at five years and 53 percent at ten years. No patient had patella baja postoperatively. There were six complications: four superficial wound infections, one superficial-vein thrombosis, and one delayed union (union occurred at five months). CONCLUSIONS: High tibial osteotomy has been criticized because of a high rate of complications, a loss of effectiveness with time, and the difficulty of conversion to a total knee arthroplasty secondary to patella baja. In our series, in which an osteotomy was performed with a calibrated osteotomy cutting guide and rigid internal fixation and was followed by early motion, the rate of complications was low and approximately two-thirds of the knees had a good or excellent clinical result at an average of 8.5 years. Conversion to a total knee arthroplasty was accomplished without difficulty in the patients who had this procedure. We highly recommend high tibial osteotomy with a calibrated osteotomy cutting guide, rigid internal fixation, and early motion for patients who wish to continue an active lifestyle.

The safety and efficacy of laparoscopic live donor nephrectomy: a systematic review.

BACKGROUND: The aim of this systematic review was to compare the safety and efficacy of laparoscopic live donor nephrectomy with the "gold" standard of open live donor nephrectomy. SEARCH STRATEGY: Three search strategies were devised to enable literature retrieval from the Medline, Current Contents, Embase, and Cochrane Library databases up until, and including, February 2000. STUDY SELECTION: Inclusion of a report was determined on the basis of a predetermined protocol, independent assessment by two reviewers, and a final consensus decision. English language reports were selected and acceptable study designs included randomized-controlled trials, controlled clinical trials, case series, or case reports. Each report was required to provide information on at least one of several safety and efficacy outcomes as detailed in the protocol. DATA COLLECTION AND ANALYSIS: Twenty-five reports met the inclusion criteria. They were tabulated and critically appraised in terms of the methodology and design, sample size, outcomes, and the possible influence of bias, confounding, and chance. RESULTS: High level evidence comparing the safety and efficacy of laparoscopic live donor nephrectomy with open donor nephrectomy was not available at the time of this review. Limited low level evidence suggested that the laparoscopic approach might be advantageous regarding the donor's hospital stay, convalescence, pain, and resumption of employment. CONCLUSIONS: The ASERNIP-S Review Group concluded that the evidence-base for laparoscopic live donor nephrectomy was inadequate to make a safety and efficacy recommendation. Clinical and research recommendations were developed regarding the introduction and current practice of this procedure in Australia.

Expression and partial purification of a recombinant secretory form of human liver carboxylesterase.

Serine-dependent carboxylesterases (EC 3.1.1.1) are found in a variety of tissues with high activity detected in the liver. Carboxylesterases (CaE) hydrolyze aliphatic and aromatic esters, and aromatic amides, and play an important role in the detoxification of xenobiotic chemicals that contain organophosphate (OP) compounds. The detoxifying ability of CaE is limited by its low concentration in serum where it encounters OP compounds. Studies in our laboratory have shown that a pRC/CMV-hCaE plasmid construct, stably integrated into 293T cells, expresses a human liver CaE in culture. However, the enzyme remained inside the cell and reached a low steady-state level of expression. The goals of this study were to overexpress a functional human liver CaE from a recombinant cDNA in a human cell line and to isolate and purify the recombinant protein. To accomplish these goals, a single amino acid change was made in the C-terminal retrieval signal, HIEL (His-Ile-Glu-Leu), of human liver CaE. The mutation produced a unique Eco47III restriction site, which aided in clone selection. The recombinant plasmid, pRc/CMV-mhCaE, was isolated and stably integrated into human 293T cells. Expression of the altered cDNA resulted in secretion of an active CaE up to levels of 500 enzyme units per liter of growth medium. Secretory CaE displayed isoelectric focusing patterns similar to those of the native enzyme with no observable changes in activity. The secreted enzyme was partially purified by hydrophobic interaction chromatography and Cibacron blue affinity chromatography. Partial enzyme purification was achieved, and CaE retained a high level of enzymatic activity.

Inhibition of gene expression by the Ggamma 5' flanking region of the Bantu beta(s) chromosome.

Beta(s)-chromosome haplotypes are peculiar to specific regions of Africa and Asia and are associated with the occurrence of different fetal hemoglobin (Hb) levels in sickle cell patients. Among these haplotypes, beta(s)-chromosomes found in the Senegal and the Arab-India regions are associated with relatively high levels of HbF expression, whereas those around the Benin, Bantu, and the Cameroon regions show low levels of HbF expression. The roles of 5'HS2 and the 5' flanking (promoter region) region in the expression of globin genes are well documented. Haplotype specific variations are found in these regions and have been postulated to be involved in the regulation of HbF expression. In this study, we have analyzed the effect of sequence variations in regulatory regions of the Bantu 5'HS2 and 5' flanking region of the Ggamma gene on CAT expression. A diminution was observed in K562 cells when the promoter originated from the Bantu beta(s) chromosome. The decreased expression was independent of the origin of the 5'HS2 sequence--combinations of the Bantu promoter were measured with the Benin, Bantu, or Senegal 5'HS2 sequences in K562 cells. However, expression of the same plasmids in murine erythroleukemic (MEL) cells showed no difference in CAT expression among the various sequence combinations studied.

Porous-coated metal-backed patellar components in total knee replacement. A postmortem retrieval analysis.

The use of porous-coated metal-backed patellar components to achieve consistent fixation by bone ingrowth and to provide relief of pain warrants serious scrutiny. We conducted a quantitative postmortem investigation of eleven consecutively retrieved components with use of high-resolution contact radiographs, electron microscopy, and histological analysis. The implants had been in situ for a mean (and standard deviation) of 45+/-36 months (range, one to eighty-four months). Analysis of the high-resolution contact radiographs revealed that a mean of 86+/-12 per cent (range, 61 to 100 per cent) of the porous coating was in contact with the host bone. Backscattered electron imaging showed that the mean volume fraction of bone ingrowth was 13+/-9 per cent (range, 0 to 30 per cent). No significant difference was detected, with the numbers available, between the volume fraction of the bone ingrowth measured in the porous coating and that of the host cancellous bone in the patellae.

Host-bone response to porous-coated cobalt-chrome and hydroxyapatite-coated titanium femoral components in hip arthroplasty. Dual-energy x-ray absorptiometry analysis of paired bilateral cases at 5 to 7 years.

Uncemented porous-coated cobalt-chrome femoral stems have produced satisfactory short-term clinical results, although slightly inferior to the results of cemented total hip arthroplasty. Proximal femoral bone resorption, osteolysis and fibrous ingrowth have been reported with porous-coated stems. Hydroxyapatite-coated stems and titanium stems have been introduced to avoid these findings through improved fixation. Dual-energy x-ray absorptiometry allows quantitative examination of bone density changes after uncemented total hip arthroplasty. This study examines the host-bone response to hydroxyapatite-coated titanium and porous-coated cobalt-chrome stems of identical geometry in three paired bilateral cases at 5 to 7 years. Distinctly different patterns of femoral bone mineral density changes were observed with the two stem designs. The authors conclude that dual-energy x-ray absorptiometry is a promising technique allowing noninvasive analysis of uncemented stem fixation, and that the data from this study suggest improved fixation and stress transfer with hydroxyapatite-coated titanium stems.

Two mutations in the locus control region hypersensitivity site-2 (5' HS-2) of haplotype 19 beta s chromosomes alter binding of trans-acting factors.

There are five major haplotypes associated with sickle cell anemia (SS). Individuals homozygous for haplotypes 3 (Senegal) and 31 (Saudi Arabian) have high fetal hemoglobin (HbF) levels (15 to 30% of total hemoglobin) whereas individuals homozygous for haplotypes 17 (Cameroon), 19 (Benin), and 20 (Bantu) have low HbF levels (1 to 10%). We previously identified several point mutations in the LCR 5'HS-2 that were specific for haplotype 19 beta s chromosomes (compared to the GenBank HUMHBB reference sequence, T-->G at position 8580, A-->G at position 8598, and A-->T at position 9114). We postulated that one or more of these mutations may alter the binding of specific trans-acting factors and ultimately affect the expression of HbF in these sickle cell patients. We performed gel mobility shift assays using 32P-end-labeled double-stranded 19mers corresponding to each of the LCR 5'HS-2 normal (GenBank) and mutant sequences. Nuclear extracts prepared from HeLa and HEL cells were used in our experiments and neither the normal nor mutant sequence at position 8580 bound trans-acting factors in either nuclear extract. The 8598 mutant increased binding of Sp1; using purified protein and both nuclear extracts. HEL extracts were used to quantify the increase in Sp1 binding to the 8598 mutation and we found an increase in binding of 66 and 47%, respectively, in two shifted bands. The 9114 mutation sharply decreased binding of an unknown trans-acting factor by 74%. This factor was present in both HeLa and HEL nuclear extracts.

A comparison of blood loss and transfusion requirements in total knee arthroplasty with and without arterial tourniquet.

A retrospective study was undertaken to determine the intraoperative blood loss and the subsequent need for blood transfusion in primary total knee arthroplasty. Fifty-six patients were operated on with the use of an arterial tourniquet (group 1), and 50 patients, without the use of a tourniquet (group 2). The mean intraoperative blood loss was significantly different between the two groups (P = 0.001). The 1-hour postoperative hemoglobin decrease was also significantly different between the two groups (P = 0.006). Thirty-four patients (61%) in group 1, and 32 patients in group 2 (64%) required a blood transfusion prior to discharge from the hospital. This difference was not significantly different. Although intraoperative blood loss was increased in the group when no tourniquet was used, the overall incidence of transfusion was the same between the two groups. It may therefore be justified to question the routine use of a tourniquet during total knee arthroplasty.

Abdominal surgery in HIV/AIDS patients: indications, operative management, pathology and outcome.

Despite the increasing number of patients with the human immunodeficiency virus (HIV) infection, surgical experience with these patients remains limited. A retrospective review over a 9 year period (January 1985 to December 1993) was undertaken to determine the indications, operative management, pathologic findings and outcome of major abdominal surgery in these patients. A total of 51 procedures were performed in 45 patients; 30 patients had acquired immunodeficiency syndrome (AIDS) and 15 patients had asymptomatic HIV infection. Indications included gastrointestinal bleeding, complicated pancreatic pseudocysts, cholelithiasis, bowel obstruction, immune disorders, acute abdomens, elective laparotomy, colostomy formation, menorrhagia and Caesarean section. Pathologic findings directly related to the HIV infection were found in 81% of the AIDS patients and 35% of the asymptomatic HIV infected patients (P < 0.05). These included opportunistic infections, non-Hodgkin's lymphoma, Kaposi's sarcoma, immune disorders, lymphadenopathy and pancreatic pseudocysts. It was noted that AIDS patients had more complications than asymptomatic HIV infected patients with most complications related to chest problems and sepsis (61 vs 7%; P < 0.01). Emergency operations carried a higher complication rate than elective operations though this was not significant. The hospital mortality was 12%. On follow up, 13 of the 25 AIDS patients had died with the median survival of 7 months, while three of the 14 asymptomatic HIV infected patients had died with the median survival of 40 months. Of the remaining patients, the 12 AIDS patients had a median postoperative follow up of 7 months and the 11 asymptomatic HIV infected patients had a median postoperative follow up of 29.5 months.(ABSTRACT TRUNCATED AT 250 WORDS)

Perioperative stroke after carotid endarterectomy. Etiological risk factors and management.

291 patients were subjected to carotid endarterectomy from January 1985 to June 1992 in two Australian medical institutions. Of the 291 patients, perioperative stroke occurred in 22 (6.3%) after 347 operations (moderate 17 and severe 5). The 22 patients were studied with Doppler scan, angiography, reexploration and CT. Reexploration showed that 12 of 14 patients had thrombosis in the internal carotid artery at operation. The etiological factors for perioperative strokes included thrombosis at the operative sites in 14 patients (64%), cerebral embolism after operation in 4, clamping ischemia in 2, intracerebral hemorrhage in 1 and unknown cause in 1. Six patients (27%) recovered completely in 4 weeks, 10 (45%) had mild residual neurological deficits, 5 (23%) had moderate neurological deficits and 1 died 3 days after operation. Only 6 patients had permanent neurological deficits (6/347, 17%).

Rationale and clinical application of hydroxyapatite coatings in pressfit total hip arthroplasty.

Although the long-term clinical results of cemented total hip arthroplasty are quite good, there is a significant problem with failure after approximately 10 years, especially with younger patients. Uncemented total hip arthroplasty has been developed in response to prosthesis loosening due to cement fragmentation and osteolysis. Porous-coated hip stems have been used, with generally promising results. However, clinical studies of porous-coated prostheses have revealed findings of concern such as thigh pain, subsidence of the femoral prosthesis, and radiographic lucencies at the bone-prosthesis interface. Hydroxyapatite coatings were developed to improve the fixation of uncemented prostheses. This article discusses the chemical, mechanical, and biological properties of hydroxyapatite coatings, and reviews the biologic behavior of experimental hydroxyapatite-coated implants. The clinical and radiographic results of a 4-year prospective trial are presented. The authors conclude that the reported experimental evidence, as well as the early clinical experience of this series and others, support the continued clinical evaluation of hydroxyapatite-coated titanium for total hip arthroplasty in younger, active patients.

Multivariate Cox regression analysis of covariates for patency rates after femorodistal vein bypass grafting.

Multivariate Cox regression analysis of patency rates for 750 consecutive femorodistal autogenous vein graftings for chronic lower limb ischemia showed that significant independent prognostic covariates were the type of graft (long saphenous or arm vein), presence of diabetes, and absence of a past history of myocardial ischemia. Analysis assumes that patients withdrawn with patent grafts due to death or loss to follow-up would have followed the same course as those who remain, and the degree to which this could distort results was studied. Patients who died with patent grafts were more likely to have had past myocardial ischemia and critical lower limb ischemia. Cox regression analysis for 600 operations after excluding patients who died with patent grafts then showed that significant independent covariates were the type of graft (long saphenous or arm vein) and indication (claudication or critical ischemia); then age, sex, hypertension, diabetes, myocardial ischemia, date of operation, surgeon, site of distal anastomosis, or first compared to repeat operations had no significant influence. Cox regression analysis helps determine which covariates influence graft patency rates, but results are affected by censored data, particularly from patients who die with patent grafts.

The discovery of anti-epileptic drugs.

The general history of epilepsy is well documented, there being detailed accounts from ancient times in Babylonia (Wilson et al., 1990), ancient India (Bharucha & Bharucha, 1989), and China (Lai & Lai, 1991), up until the end of the 19th century (Tempkin, 1971). But relatively little has been written about its medical treatment, (Melville, 1982). The subject of this article is the history of potassium bromide, phenobarbitone and phenytoin, how their use in epilepsy was discovered, and in particular the surprisingly large part played by chance, luck and serendipity, in their introduction to the pharmacopaeia. The advance in this field has been one of sudden leaps forward, followed by periods of apparent inactivity, until the next discovery emerged, a pattern repeated many times, since medical treatment of epilepsy began with potassium bromide in 1857, until the introduction of vigabatrin in 1990.

Neurogenic claudication secondary to vascular disease.

Neurogenic claudication is characterized by sensory symptoms which appear during exercise or while maintaining a fixed posture. They are paraesthetic in quality, may be associated with 'march' phenomena, and patients may have bowel and bladder disturbance. The problem is most commonly secondary to lumbar canal stenosis (LCS) but rarely due to aortic disease, as shown in this case report. This report concerns a 66 year old woman who presented with symptoms of paraesthesia radiating from the buttocks to the thigh and, intermittent loss of bladder and bowel function, all associated with walking. There were no associated symptoms of vascular claudication. Clinically, there was evidence of aorto-iliac obstruction with absence of femoral pulses and a vascular index of 0.4 at both ankles. Neurological examination was normal at rest but the left ankle jerk was absent immediately after exercise. Myelogram and computerized tomographic (CT) scan were normal. An aortogram revealed a very tight irregular stenosis of the aorta at the level of the renal and mesenteric arteries. Very few lumbar vessels were seen. An aortic endarterectomy via a thoraco-abdominal approach was performed and an aortobifemoral graft inserted. The patient's symptoms resolved following this procedure. We postulate that her symptoms were caused by a 'steal' from the blood supply to the cauda equinda due to the severe athromatous disease of her upper abdominal aorta.

In vivo heparin response and consumption in patients before and during arterial reconstructive surgery.

This study investigated the effects of heparin in patients with peripheral arterial disease, before and during operation. The relation between heparin dosage and heparin response and consumption were calculated from changes in the activated clotting time (ACT). Before operation, 38 patients were each given 10,000 units of heparin by intravenous injection and ACT was measured after 5, 10, 20, 30 and 60 minutes. Assuming a linear relation between heparin dosage and ACT, a dose of heparin was calculated which should double the normal ACT. This was given during operation in 21 patients while a standard dose of 7,500 units of heparin was given to another 10 patients. ACT was measured during operation at the same time intervals as before operation. ACT was always at its highest level at the 5 minute test and was always still raised at 60 minutes, both before and during operation. No significant correlation was found between ACT, heparin response or heparin consumption, and the patients' ages, sex, body weights and creatinine levels, either before or during operation. It was not possible to predict the intraoperative response from the preoperative test. It is concluded that the heparin effect should be monitored during operation in each patient if the best dose response is to be obtained.