Ethnic differences in salt sensitivity: genetic or environmental factors? 1. The CARDIAC study, a world-wide cross-sectional epidemiological study on the relationship between alimentary factors and cardiovascular diseases, provided the initial evidence of ethnic differences in salt sensitivity; this was because despite much less urinary sodium excretion in Tanzania than in Brazil and the Japanese, the prevalence of hypertension was relatively higher in Tanzania than in the latter two populations. 2. To investigate this difference in salt sensitivity, a standardized clinical experiment was carried out: six to 13 male volunteers were placed on 2500 kcal basal diets containing 3 g salt/day. Eighteen grams of salt were added daily from the sixth to the 11th day in Tanzania and Brazil, while 22 g of salt were added in Japan. 3. Salt loading induced a significant rise in systolic blood pressure (SBP) on the second day of the high salt period (HSP) in Japan, the second and third day of HSP in Brazil, and all days of HSP in Tanzania. 4. Salt sensitivity was seen in 16.7% of the participants in Japan, 36.4% in Brazil and 46.2% in Tanzania. Further analysis of the effect of salt on blood pressure (BP) was carried out using the data from the CARDIAC study by multiple regression analysis. A within-centre comparison of fatty acid was also made. 5. The regression analysis revealed that the relationship of salt and blood pressure is more positively tight in Tanzania than Brazil and Japan after controlling for other confounding variables. Fatty acids in serum phospholipids contain significantly more palmitic acid and showed lower P/S ratios than those from Brazil and Japan.


Quantitative analysis of the tracking of blood pressure and relative factors in childhood: Shimane Heart Study. 1. In order to clarify the predictive factors of cardiovascular diseases caused by hypertension and hypercholesterolaemia in adults, a longitudinal epidemiological study was started in 1978. 2. This paper reports the results of research carried out from a quantitative analysis of the tracking of blood pressure and anthropometric parameters in children and adolescents using a tracking index. The index was calculated according to the changes in blood pressure quintiles for the whole population during the observation period. 3. The study population consisted of 5148 Japanese children living in the city of Izumo, who were examined every 3 years between the ages of 6 and 15 years old. 4. Although systolic blood pressure tracked weakly during childhood and adolescence, there was no significant relation between the tracking of systolic blood pressure and a family history of hypertension. 5. The tracking indices of the anthropometric parameters were better than those of systolic blood pressure, but the index of the left ventricular mass was similar to that of systolic blood pressure. 6. In conclusion the tracking of blood pressure might be determined by the tracking of bodyweight and height.


Family history study on hypertension in Japan. 1. Familial aggregation of hypertension was determined in 187 Japanese nuclear families. The necessary data on family and case history particularly concerning the hypertensive status were obtained by personal interviews of outpatients at six local hospitals, using a specifically designed questionnaire. 2. From the family history of the 187 living index children (single ascertainment), 134 pairs of parents were informative. Of 819 children, excluding index cases, the number of hypertensives, normotensives and status unknown were 224, 274 and 187, respectively. Individuals under 30 were classified as unknown. 3. For a child given the birth order, empirical risk to be hypertensive was calculated from the proportion of hypertensives to normotensives plus hypertensives. 4. Irrespective of parental mating types, among a simplex family of hypertension the index cases of the first-born child were more than the others. 5. There was no birth order effect in risk among multiplex families of hypertension. 6. There was no increase of hypertensive offsprings observed when the mother was hypertensive.


The immune system in health and disease. For an immune response against an eliciting antigen, innate and adaptive immune mechanisms interact to provide a specific and appropriate response characterized by self-non-self discrimination and memory. This non-random process involves antigen presentation followed by T cell recognition and activation with the elaboration of T cell-derived lymphokines. The nature and amount of lymphokine production from antigen-activated T cells then determines the predominant immune response (e.g. cytotoxicity versus antibody). Exogenous regulatory factors, including steroid hormones, prostaglandins, and cytokines, modulate immune responsiveness. How these regulatory factors influence the immune response during specific host-parasite interactions determines the predominant immune response to specific antigen. As the regulation of the immune response is unravelled, new and powerful immunomodulatory therapies will be developed and utilized to improve the immune response and host survival.


The normal fetomaternal immune relationship. The antigenic status of the preimplantation embryo is ill-defined and there are no clearly recognized maternal immune reactions against this early stage of development. Following implantation, the pregnant female shows evidence of immune recognition of her intrauterine allogeneic conceptus. In a proportion of pregnancies, particularly in multiparous women, there are maternal cytotoxic antibodies exhibiting specificity for the paternally inherited HLA antigens of the fetus. When these are undetectable there may be other antibodies that are non-complement fixing and non-cytotoxic or antibodies that are not present as free molecules and incapable of identification in conventional assays. Anti-HLA antibodies pose no threat to the fetus, principally owing to their absorption by the placenta and, very likely, the harmless binding of any that do reach the fetal circulation. No potentially deleterious cytotoxic T lymphocyte generation occurs in most pregnancies. The extent to which this is due to maternal immunoregulatory control processes is not yet established. The fetal trophoblast is able to act as a protective barrier by virtue of unique properties, including a lack of conventional class I and class II HLA molecules, that render it insusceptible to immune attack. The nature and significance of any maternal recognition of non-HLA antigens on trophoblast await elucidation. Maternal immune cell traffic across the placenta occurs only at a very low level, if at all, in normal pregnancy. This may take place to a greater degree in some of the rare instances of fetal graft-versus-host disease, but this is complicated by the associated fetal immunodeficiency. Maternal IgG antibodies are transmitted across the placental trophoblast by receptor-dependent mechanisms to provide immediate protection for the neonate against environmental pathogens. Leakage of fetal erythrocytes, leukocytes and platelets into the maternal circulation can elicit IgG isoantibodies that take advantage of the same mechanisms to gain access to the fetus, with pathological consequences. Autoantibodies in women with various disease states may similarly pass into the fetus but these normally produce only mild and transient effects. The development of the fetal immune system begins at an early stage of gestation. It is competent to respond to intrauterine infections from as early as 12 weeks and has full functional potential at birth. Maternally acquired IgG is available for up to 9 months of life until the infant's own immune system has been adequately primed and activated following first exposure to specific antigens. The normal fetomaternal immune relationship represents a remarkable harmonious association between two genetically disparate individuals.(ABSTRACT TRUNCATED AT 400 WORDS)


Complement and pregnancy: new insights into the immunobiology of the fetomaternal relationship. Recent studies have revealed that human trophoblast expresses three membrane-bound proteins which function specifically to regulate the activity of complement. These proteins are already known to be widely distributed in normal adult tissues where they protect host cells from damage resulting from the fortuitous deposition of activated complement components. Their activities are focused at two distinct steps in the complement pathway. Decay accelerating factor (DAF, CD55) and membrane co-factor protein (MCP, CD46) act at the level of the C3 convertase enzymes which activate C3 to C3b. A further protein, CD59, directly regulates the formation and function of the terminal cytolytic membrane attack complex (MAC) by specifically interacting with C8 and C9. These proteins appear to play an important role in the maintenance of normal human pregnancy. DAF, MCP and CD59 are all expressed where trophoblast surfaces are in contact with maternal blood and tissues and expression occurs from at least 6 weeks of gestation. The semi-allogeneic human conceptus therefore appears to be effectively protected from maternal complement-mediated damage arising either from alternative or classical pathway activation or in a bystander fashion following a response to microbial infection in the mother. Complement regulatory protein deficiency disorders with clinically demonstrable consequences especially in terms of haemolytic disease are known to exist and have proved valuable in establishing the biological role of these proteins in vivo. The demonstration of this new family of immunoregulatory proteins on trophoblast raises important questions about the potential involvement of these products in pregnancy pathologies.


Alloimmune conditions and pregnancy.

Alloimmune conditions and pregnancy. Transfer of fetal red blood cells and platelets to the maternal circulation can stimulate an immune response with production of immunoglobulin that can cross the placenta. Similarly, passage of maternal stem cells to an immunologically incompetent fetus can theoretically produce graft-versus-host disease. disease. Maternal sensitization to red blood cell antigens such as D and Kell can result in anaemia, hydrops, and death in an incompatible fetus. Current assessment of these pregnancies involves serial analysis of amniotic fluid bilirubin concentration, with umbilical cord blood sampling reserved for special circumstances; neither ultrasound or Doppler blood flow analysis are accurate in the prediction of fetal haematocrit. Intravascular transfusion is the treatment of choice for hydropic fetuses. Perinatal survival in non-hydropic fetuses is similar with either intravascular or intraperitoneal transfusion, and the choice of procedures is individualized. Isoimmune fetal thrombocytopenia is usually the result of maternal sensitization to the PlA1 antigen. There is significant risk of intracranial haemorrhage, both antepartum and during labour and delivery. Umbilical cord blood sampling at term can determine fetal platelet count and the need for platelet transfusion, and can aid in deciding the appropriate route of delivery.


Immunological aspects of pre-eclampsia.

Immunological aspects of pre-eclampsia. The first pregnancy preponderance and apparent partner specificity of pre-eclampsia suggest that it might have an immune aetiology. The pathogenesis of pre-eclampsia is undefined although it is clear that it is a placental disorder. The maternal syndrome appears to be mediated by placental ischaemia secondary to spiral artery insufficiency. This leads to a hypothesis that pre-eclampsia is a two-stage disease. The first comprises processes that limit the size of the spiral arteries (poor placentation) or obstruct them (acute atherosis). Either or both may have immunological causes although there is no direct evidence. Factors limiting placentation could involve maternal immune intolerance of the fetal allograft, which in their most extreme expression could lead to immunologically mediated abortion. Thus pre-eclampsia may be part of a wider spectrum of pregnancy loss secondary to poor maternal immune accommodation of her genetically disparate fetus. The second stage involves the consequences of the ensuing placental ischaemia. The syndrome is currently tentatively ascribed to diffuse maternal endothelial dysfunction. There is less reason to invoke immunological mechanisms in the second stage although neutrophil activation could explain generalized endothelial damage. It should be clear that these conclusions are provisional and that the greatest need is for more investigation to eliminate the uncertainty which clouds our concepts.


Contraception.

Contraception. The principle of vaccination for the purposes of fertility regulation is scientifically elegant and socially compelling. Factors such as economic production, convenience of use, relatively long-lasting but reversible protection, low failure rate and the avoidance of mechanical devices or exogenous hormones make this approach a potentially attractive option for family planning programmes in both developing and developed countries. The major efforts in research and development have involved the prospect of active immunization against specific antigens of sperm, oocyte, zygote and early embryo, and the pregnancy hormone human chorionic gonadotrophin (hCG). Several anti-hCG vaccines have entered clinical trials. They operate by preventing or interrupting pregnancy at the peri-implantation stage probably by neutralizing the luteotrophic effect of hCG. The most refined vaccine is one directed against the unique C-terminal peptide on the beta-subunit of hCG. This vaccine provokes antibodies that are specific for hCG and do not cross-react with human luteinizing hormone (hLH). Preclinical studies in baboons and data from a phase I human trial indicate that this method is free of side-effects and provides the promise of a duration of effectiveness of up to 12 months. Future research will optimize the anti-hCG approach, utilize new vaccine delivery systems and broaden the spectrum of target antigens of potential utility for contraceptive vaccines.


Hydroxylapatite-coated hip implants. Multicenter three-year clinical and roentgenographic results. The application of a thin coating of hydroxylapatite to total hip implants has provided the opportunity to realize stable fixation of a press-fit prosthesis without a porous coating or an intervening fibrous tissue layer. This series consists of 436 total hip arthroplasties, of which 320 cases have a minimum two-year follow-up period and 142 cases have a minimum three-year follow-up period. The femoral prosthesis used was a roughened titanium alloy with a 50-microns surface treatment of hydroxylapatite applied to the proximal one third. The acetabular components implanted included porous-coated implants (132), hydroxylapatite-coated acetabular shells of varying geometries (285), and bipolar implants (16). Analysis of the clinical results demonstrates a mean Harris Hip Score of 93 at six-months postarthroplasty, 95 at one and two years, and 96 at three years. At the three-year follow-up evaluation, 4.2% of patients complained of mild to moderate pain in the operative limb, whereas only 2.2% at two years and 1.4% at three years complained of activity-related thigh pain. The femoral mechanical loosening rate representing stems revised for aseptic loosening (two) plus roentgenographically unstable stems (zero) is 0.46%. Three hydroxylapatite-coated acetabular cups (1%) have shown measurable migration at two years, but none have been revised for aseptic loosening. The roentgenographic evaluation provides evidence for excellent proximal femoral fixation with distal stress transfer. Radiolucencies typically occur around the uncoated distal tip of the femoral stem (74%), but rarely in the proximal hydroxylapatite-coated anterior (3%) and lateral (2%) zones. Femoral cancellous condensation characteristically is seen at the transition zone of hydroxylapatite coated-to-uncoated stems (86%), whereas up to 32% of cases show cortical hypertrophy at the medial distal stem. These roentgenographic changes are progressive from one through three years postoperatively.


Acrylic fragmentation in total hip replacements and its biological consequences. Loosening of total joint prostheses is in part related to the fragmentation of the acrylic cement mantle surrounding the prosthesis and the biologic consequences to the particulate acrylic. Fractographic studies of femoral cement mantles retrieved at revision surgery and autopsy showed frequent fractures in varying stages of development in the cement and wear at the fracture surfaces. Defects in the cement mantle, thin mantles, sharp corners on the prosthesis, separation at the cement mantle interface, and pores in the cement were frequently associated with cement fractures. The progressive fractures and wear led to the liberation of particulate acrylic debris into the surrounding tissues. The tissues at the bone-cement interface removed at revision surgery showed that a macrophage, giant-cell foreign-body granulomatous reaction occurs in response to the particulate, but not bulk cement. This tissue can produce a variety of chemical mediators of inflammation and bone resorption, and can resorb bone in organ cultures. A granulomatous tissue reaction with a very similar appearance can be produced in experimental animals using particulate-form polymethylmethacrylate (PMMA), but not the bulk form of PMMA. The tissue reaction is not mediated by the classic cell or humeral immune mechanisms. Subcutaneous injection of particulate PMMA powder into fully immunocompetent C3Hf/SED mice as well as three strains of mice with progressive immunologic deficiencies (nude/nude, SCID, and triple deficient Nu-bg-XID/SED mice) led to a foreign-body reaction in all strains at five weeks as shown by histologic and immunohistochemical examination despite the differences in immune deficiency. This, along with the scarcity of lymphocytes in the human tissues, suggests that the biologic reactions to fragmented cement can be produced and sustained by nonimmune phagocytosis and activation by macrophages and giant cells without significant contribution by the immune system.


Mechanisms of failure of modular prostheses. The expectations of wear and longevity of total hip components are based in large part on Charnley's early work. The evolution of the total hip from the one-piece, all-polyethylene acetabular component and fixed-head femoral component to the myriad of parts that comprise many of today's total hip designs has brought with it an array of potential mechanisms for failure that were not present in the earlier design. The risk/benefit ratio of these new designs may need to be reevaluated based on the additional mechanisms for failure that they provide. One hundred eleven acetabular hip prostheses and 139 femoral prostheses, all of modular configuration, retrieved by surgeons in the field, and sent for histologic examination, were analyzed for this study. A number of component characteristics were found to be correlated to early failure. These included acetabular designs with thin polyethylene bearings, poor fixation of the polyethylene to the metal shell, and geometries that permitted a moment to be applied to the bearing insert, tending to cause it to rotate in the metal shell. Modular femoral components were observed to be susceptible to corrosion, with titanium-alloy stems mated to cast cobalt-alloy heads at greatest risk attributable to a galvanic effect. All modular connections of femoral and acetabular components are at risk for disassociation and fretting; therefore, clever design and precision machining are necessary to produce prostheses in which the benefits of modularity exceed the risks.


Quantification of implant micromotion, strain shielding, and bone resorption with porous-coated anatomic medullary locking femoral prostheses. Fourteen femora containing porous-coated anatomic medullary locking (AML) femoral prostheses were retrieved from 12 patients at autopsy. Clinical roentgenograms in 13 femora showed bone remodeling changes, indicating that the implants were fixed by osseointegration. Under simulated physiologic loading, micromotion between the implant and the bone was measured using electrical displacement transducers connected to the implant and to the adjacent cortex. The micromotion between the implants at the areas of porous coating and the adjacent cortex in the one case of failed bone ingrowth measured 150 microns. Maximum relative motion between the cortex and the implant in the areas of porous coating for the 13 cases showing signs of bone ingrowth was 40 microns, and this was completely elastic relative displacement. With all implants, the micromotion between the cortex and the stem was always greatest over the uncoated portion of the stem. Four of the implants were proximally porous coated. With these, the micromotion was greater over the uncoated areas than with more extensively coated stems and was always greatest at the uncoated tip of the prosthesis. The amount of micromotion was directly related to the extent of porous coating on the implant. Maximum tip motion for the proximally coated implants was 210 micra, whereas for the fully porous-coated implants, it was 40 microns. In nine of the autopsies, the contralateral normal femur was obtained in addition to the femur containing the AML (the in vivo remodeled femur). These were used for comparative studies of strain shielding and femoral remodeling. Cortical strains were measured in the in vivo remodeled femora and were compared with measurements made in the contralateral normal femora before and following implantation of a stem identical to that present on the clinically treated side. The data showed major strain reductions in all the postmortem implanted normal femora. Comparison of the strain data from the postmortem implanted normal femora with those from the in vivo remodeled femora clearly indicated that extensive bone remodeling did not result in restoration of cortical strain levels anywhere near normal. Strain shielding continued to exist in all of the remodeled specimens, even up to 7.5 years after surgery. This strain shielding was associated with bone remodeling changes that resulted in regional reductions in bone mineral content that ranged from 7% to 78%. These observations are unique, important, and valuable in defining the in vivo function and clinical behavior of this type of porous-coated femoral component.


Debris from cobalt-chrome cable may cause acetabular loosening. To address the issue of nonunion with trochanteric osteotomy, surgeons have experimented with various modes of fixation, wire and cable being the two most popular. From a group of 643 primary cemented total hip arthroplasties performed by a single surgeon via the trans-trochanteric approach, minimum four-year roentgenographic follow-up evaluations were performed on 322 hips (50%). The method of fixation was stainless steel monofilament wire in 162 cases and Co-Cr cable in 160. Trochanteric union rates were 75% (122 patients) for the wire group and 79% (126 patients) for the cable. Breakage rates of the entire trochanteric fixation construction (all three wires or cables) were 43% (68 patients) for the wire and 12% (20 patients) for the cable. Unraveled cable was seen in 56% of the hips (90 patients), and in 47% of these hips, there were no broken cables. Blinded roentgenographic analysis of the acetabulum, preformed independently, revealed that loosening of the acetabulum in the cable group was greater than in the wire group. Cables offer no significant benefit over wires and may have potential adverse effects. Generation of significant particulate debris was noted roentgenographically, and marked reaction/destruction was found at the time of revision surgery.


Ultrasonic technology in revision joint arthroplasty. The development of ultrasonically driven tools for revision joint arthroplasty is presented. The data represent seven-years' experience and include information from laboratory investigation and clinical experience from 20 surgical cases. Whole bone torsional strength studies reveal no decrease in strength parameters after the removal of cement ultrasonically. Comparison studies demonstrate that ultrasonic tools allow more rapid completion of cement and prosthesis removal than traditional manual tools. Histologic studies using an in vivo canine model demonstrate no deleterious effects to endosteal bone where cement had been removed by ultrasound. Clinical studies indicate that the use of ultrasound facilitates the surgery and causes no cortical perforations; the creation of cortical windows was not necessary in all cases. Ultrasound is safe and efficacious in cement and prosthesis removal during revision surgery.


Modular femoral stem removal during total hip arthroplasty using a universal modular stem extractor. Removal of a modular head femoral prosthesis may be extremely difficult during revision total hip arthroplasty (THA). A universal modular stem extractor was developed that achieves a secure attachment to the stem taper, and applies tensile forces with a five-pound slaphammer. Clinical use indicates that this new device facilitates uncomplicated modular femoral stem removal.


Segmental cement extraction at revision total hip arthroplasty. Cement removal in revision total hip arthroplasty can be technically challenging. Traditional methods involve using a combination of chisels, power burrs, and drills, as well as windowing the femoral cortex to gain access to cement distally. These methods can be associated with femoral fracture or uncontrolled cortical perforation and bone loss. A new technique had been developed that permits segmental extraction of bone cement from the femoral canal. Fresh cement is introduced into the old cement mantle and a threaded rod is placed into the wet cement and held in place while the cement hardens. The thread-forming rod is then removed leaving a threaded channel in the cement. Extraction rods are then screwed 1.5 to 2.5 cm into the threaded channel. A slap hammer, which attaches to the opposite end of the extraction rod, is used to remove 1.5- to 2.5-cm segments of cement. Fifteen cases involving revision of cemented femoral components were analyzed using this system. Complete cement removal was achieved in 12 cases with much less damage to the femur when compared with conventional methods. In two cases, there was retained cement along the medial wall of the femur and, in one case, the plug could not be extracted using this system. There were no fractures or cortical perforations in this series.


The removal of porous-coated femoral hip stems. During a ten-year period, 70 porous-coated femoral hip components of several designs were removed for various reasons. Based on this experience, techniques for the removal of porous-coated stems have evolved and are described, including a newer method for the safe removal of extensively coated bone-ingrown stems. Preoperative roentgenograms were highly predictive of fixation mode as corroborated by intraoperative mechanical testing, gross inspection, and histologic examination. Stable implants (17 bone-ingrown and 11 fibrous tissue-encapsulated) required interface access and division before their removal. Minimal bone damage was incurred, and in no case was reconstruction precluded by stem removal. There were no unplanned cortical perforations. Two minor femoral fractures occurred. The authors present an overall approach and specific surgical techniques that facilitate the safe removal of porous-coated femoral stems on a consistent basis.


Articular geometry of the glenohumeral joint. Little quantitative data exists defining the true shape of the humeral head and glenoid articular surfaces. This study uses a precise stereophotogrammetry (SPG) technique and provides highly accurate quantitative results for determining the three-dimensional geometry of glenohumeral joint articular surfaces, including their "sphericity", surface areas, cartilage thickness, and the difference in these quantities between the genders. Results indicate that glenohumeral joint surfaces may be approximated by a section of a sphere with small deviations from sphericity of less than 1% of the radius. Furthermore, results indicate that mating humeral head and glenoid articular surfaces are quite congruent and have radii within 2 mm in 88% of cases, and within 3 mm in all cases measured. The lack of anatomic stability of this joint is therefore not attributable to the relative shallowness or lack of congruence of the joint but rather to the small surface area of the glenoid which does not enclose the humeral head. Cartilage thickness results may partially explain perceptions of glenohumeral incongruity obtained from roentgenographic measurements where the glenoid appears flatter than the corresponding humeral head. Only when the actual articular cartilage surfaces are analyzed is it determined that the actual articulating surfaces do conform.


Scapulothoracic motion in normal shoulders and shoulders with glenohumeral instability and impingement syndrome. A study using Moiré topographic analysis. Qualitative visual inspection and manual muscle testing are traditional methods of evaluation that may overlook subtle weakness of the axioscapular musculature. A modification of the standard technique of Moiré topographic analysis of spinal deformity was applied to assess axioscapular muscle function in 51 subjects: 22 asymptomatic individuals, 22 with shoulder instability, and seven with impingement syndrome. Static Moiré evaluation demonstrated scapulothoracic asymmetry or increased topography in 14% of asymptomatic subjects, compared with 32% and 57% in the instability and impingement groups, respectively. The dynamic Moiré test demonstrated an abnormal Moiré pattern in 18% of asymptomatic individuals, compared with 64% and 100% in the instability and impingement groups, respectively. Axioscapular muscle dysfunction is common with both instability and impingement syndrome of the shoulder, although it remains to be determined whether this represents a primary or secondary phenomenon.


Hand and wrist function after external fixation of unstable distal radial fractures. Twenty-eight patients with 31 fractures of the distal radius were treated by closed external fixation. The complication rate for this series was 50%. Anatomic results were acceptable but hand function at final review was disappointing, particularly in the measurement of grip strength and the patient's ability to perform the activities of daily living. There was a highly significant correlation between complications and poor functional outcome. Although external fixation can achieve restoration of normal anatomy, functional outcome may be poor because of the severity of the associated soft tissue injury.


Congenital trigger digit.

Congenital trigger digit. Release of the sheath of the flexor tendon is the accepted solution for the problem of congenital trigger digits in children. A series of 27 patients with 37 trigger digits were observed over a period of 18 years: the average follow-up on these patients was 46.9 months. Thirty-two thumbs, three long fingers, and two ring fingers showed locking and a degree of triggering. Thirty-three digits required surgery. The surgical treatment is simple and effective. The outcome in most cases shows that this is a conservative approach.


Carpal canal stenosis in men with idiopathic carpal tunnel syndrome. The carpal canal and carpal bones of 14 male patients with idiopathic carpal tunnel syndrome and 26 normal male controls were examined by computed tomography. When compared with the controls, there was significant stenosis of the proximal part but not of the distal part of the carpal canal. Carpal canal stenosis is an important etiologic factor in the development of idiopathic carpal tunnel syndrome in males.


Bilateral diskoid medial menisci diagnosed by magnetic resonance imaging: a case report. A diskoid medial meniscus is a rare finding occurring in approximately 0.3% of the general population. Bilateral medial diskoid menisci are even less common, with only three other cases appearing in the literature. This may be the first reported case of bilateral medial diskoid menisci diagnosed by magnetic resonance imaging and verified at arthroscopy.


Knee extensor mechanics after subtotal excision of the patella. Two sets of six fresh frozen autopsy specimens were used to test the quadriceps force requirements for knee extension after sequential distal-to-proximal and proximal-to-distal excisions of the patella. The quadriceps force as a function of knee flexion angle was recorded for varying amounts of excision and compared with the results for total patellectomy. Excision of the proximal one half or less resulted in lower force requirements when compared with total patellectomy. The effects of removal of the proximal three-fourths length of patella were inconsistent and actually increased the force requirements in three knees. The effects of distal to proximal excisions indicate a biomechanical advantage to maintaining a fragment equal to at least three fourths the length of the proximal patella. Retaining a fragment of adequate size preserves at least some of the mechanical advantage provided by the intact patella.


Fractures of the femur treated by intramedullary nailing using the fluted rod. A report of 193 consecutive cases. One hundred ninety-three of 196 acute nonpathologic femoral shaft fractures were treated consecutively with intramedullary nailing using the fluted rod. Closed intramedullary nailing was used in 126 fractures, and an open technique was used in 67. This series includes 58 open fractures and 104 comminuted fractures. All fractures treated with the fluted rod united. Complications included three superficial infections (1.5%). Malrotation greater than 20 degrees was noted in six patients (3.1%). Significant shortening (5 cm), which required treatment, occurred in one patient. After initial resuscitation and evaluation, routine treatment included preoperative traction and a first-generation cephalosporin followed by accurate reduction and nailing of the fracture. The results of this series suggest that the fluted rod may be ideal for the treatment of most femoral shaft fractures.


Olecranon fractures. A clinical and radiographic comparison of tension band wiring and plate fixation. Forty-one adult patients with displaced olecranon fractures were treated with open reduction internal fixation in a prospective, randomized study comparing tension band wiring (TBW) and plate fixation (PF). Plate fixation required longer operative time, but did not lead to an increased complication rate. Range of elbow motion at six months did not differ significantly between the two groups. Symptomatic metal prominence was frequently observed after TBW (42%), although true Kirschner wire (K-wire) migration was seen in only one patient. Postoperative loss of reduction, leading to a significant articular step-off or gap, was more frequent after TBW (53%) than after PF (5%). Tension band wiring resulted in 37% good clinical and 47% good roentgenographic results, as compared with PF, which resulted in 63% good clinical and 86% good roentgenographic results. Plate fixation should be carefully considered when planning open reduction and internal fixation of displaced olecranon fractures.


Intramedullary nailing of tibial nonunions. Fifteen tibial nonunions, ranging nine months to 19 years after original injury, were treated with the Brooker intramedullary nail (IMN). The average number of previous failed surgeries was two. The fracture location ranged from several centimeters below the tubercle to 3 cm above the plafond. Twelve of 15 had bone grafting, and all 15 had fibular osteotomy at the time of the IMN procedure. Thirteen of 15 were reamed, and 11 of 15 were nailed open. Patients required an average of five postoperative days in the hospital, and 14 of 15 tibial nonunions healed uneventfully at an average of eight months after the IMN procedure. Weight bearing in a removable patellar-tendon-bearing (PTB) brace was encouraged in most cases by two to four weeks postoperative. One nonunion patent, traumatically refractured after rod removal, was treated at another hospital with dynamic compression plating and iliac crest bone graft; the fracture healed three months later but was considered an IMN treatment failure. There were no other significant complications. The IMN procedure encourages early return to function and reliably promotes union in even the most challenging and complex of tibial healing problems.


Experimentally produced ankle fractures in autopsy specimens. Twenty-six unembalmed lower-leg specimens were mounted in an experimental test device with the foot placed at a fixed degree of pronation/supination, dorsiflexion/plantar flexion, or both. Torque versus rotation curves were determined as each foot was externally rotated to failure. Torsional stiffness was determined for the first 20 degrees of external rotation, and energy to failure was noted at the point of initial failure. Anatomic dissection and roentgenographs delineated the degree of injury in all specimens. Gender had the greatest effect on both torque and energy parameters, and the injury pattern. In males, 67% of specimens had an oblique fibular fracture, torn anterior tibiofibular ligament, and torn deltoid ligament (SER2). In females, 45% had a transverse fibular fracture without syndesmotic or deltoid injury. Forty percent of females had the SER2 injury. Angle of supination/pronation did not correlate with a specific injury pattern. Peak axial load had a significant effect on stiffness, but increasing the load by more than three times body weight did not increase injury severity.


The articular manifestations of Paget's disease of bone. A case report. Disorders of joints are commonly associated with Paget's disease of bone but are often disregarded or attributed to the underlying Pagetic condition. The authors evaluated a 69-year-old man with extensive Paget's disease of bone, degenerative arthritis, calcific periarthritis, and gout. The degenerative arthritis and calcific periarthritis of the shoulders was originally mistaken for Paget's disease of the proximal humerus. The wrist arthritis was attributed to Paget's disease until evaluation of surgical pathology specimens showed intraarticular gouty granulomas. In evaluating and treating a patient with Paget's disease of bone, the orthopedic surgeon should be aware that the successful treatment of associated articular disorders may require therapeutic measures in addition to those used in treating the Paget's disease.


In vitro bone-cell response to a capacitively coupled electrical field. The role of field strength, pulse pattern, and duty cycle. Newborn rat calvarial bone cells were grown to confluence and subjected to a matrix of sine wave 60-kHz capacitively coupled electrical signals of various field strengths, pulse-burst patterns, and duty cycles. Both [3H] thymidine incorporation into DNA and alkaline phosphatase activity were evaluated in field strengths ranging from 0.0001 to 20 mV/cm, with pulse-burst patterns ranging from continuous to 5 milliseconds ON/495 milliseconds OFF, with daily duty cycles ranging from 0.25% to 25%. A significant increase in proliferation occurred in field strengths of 0.1, 1, and 20 mV/cm when the signal was applied continuously for six hours. Significant proliferation also occurred when the 20-mV/cm field was pulsed for six hours at 5 milliseconds ON/495 milliseconds OFF and at 5 milliseconds ON/245 milliseconds OFF. No change in alkaline phosphatase activity occurred in the 20-mV/cm field with any signal. At 1 mV/cm, there was a significant decrease in alkaline phosphatase activity in the continuous signal and in the 5 milliseconds ON/62 milliseconds OFF signal; in the lower fields evaluated, there was an actual decrease in alkaline phosphatase activity with some of the signals. The field strength plays a dominant role in determining the bone-cell's proliferative response, and to a lesser extent the alkaline phosphatase activity response, to a capacitively coupled electric field. The pulse configuration and the duty cycle are also important, but only if the proper field strength is being applied to the cell.


Changes in somatosensory-evoked potentials in limb lengthening. An experimental study on rabbits' tibiae. To assess the influence of the rate and amount of distraction on the electrophysiologic function of the peripheral nerve during limb lengthening, somatosensory-evoked potential (SSEP) studies were performed on the hindlimbs of 96 rabbits. In Group I, the tibiae were lengthened 0.35 mm per day; in Group II, 0.7 mm per day; in Group III, 1.05 mm per day; and in Group IV, 1.4 mm per day. The studies were done preoperatively and then postoperatively, until six weeks in Group I, five weeks in Group II, four weeks in Group III, and three weeks in Group IV. As lengthening proceeded, the P1 (the first major positive peak) latency gradually increased, whereas the amplitude decreased. Significant amplitude changes were observed at six-weeks postsurgery in Group I, three weeks in Group II, two weeks in Group III, and one week in Group IV. Significant changes in P1 latency were observed at four weeks postsurgery in Group II, three weeks in Group III, and two weeks in Group IV. Greater percentage increases in tibial length corresponded to more marked changes in P1 latency and amplitude. The SSEP monitoring may serve as an effective tool for early detection of neurologic dysfunction during limb lengthening.


A comparison of magnetic resonance imaging to bone scintigraphy in early traumatic ischemia of the femoral head. In adult rabbits, a unilateral subcapital osteotomy of the femoral neck was performed to induce avascularity. One half of the osteotomy sites were fixed with a magnetic resonance imaging (MRI) compatible absorbable pin and the other osteotomies had no fixation. The femoral heads were studied at three, five, and 12 days with roentgenographs, bone scintigraphy, and MRI, and MRI only at four weeks and six weeks after osteotomy. Histologic studies were performed after imaging to evaluate the viability of the femoral heads. At three, five, and 12 days after osteotomy, bone scintigraphy showed a decrease in uptake of radioisotope in the region of the femoral head on the operated side relative to the acetabulum and greater trochanter in 17 of 18 rabbits. A comparison of the surgically treated hip to the normal hip in fixed and unfixed osteotomies showed no change in the signal behavior of T1- or T2-weighted images in all rabbits Days 3, 5, and 12 (n = 18) after operation. The rabbit femoral heads with fixation of the osteotomy 28 days after operation showed a decrease in signal intensity in the subcapital region of the femoral head. Six weeks after operation, the fixed femoral head shows a loss of signal in a portion of the femoral head near the osteotomy. The MRI signal intensity appears to increase in the unfixed femoral heads six weeks after operation.(ABSTRACT TRUNCATED AT 250 WORDS)


Cortical strut allografts in the reconstruction of the femur in revision total hip arthroplasty. A basic science and clinical study. Repeated total hip arthroplasties cause a loss of bone stock that will produce diminished component support, and can compromise implant function. There is, therefore, a compelling argument to return bone stock to the femur at the time of revision arthroplasty. Cortical strut allografts serve this purpose. They unite consistently and reliably, by 8.4 months on average. The overall rate of strut union is 96.6%. The sequence of healing events starts with round-off, followed by partial bridging and complete bridging. The repair process includes remodeling of the host femur, as well as the graft. Although there is variable resorption of some grafts, usually where not opposed to the host bone, there is also extension of others from host callus build-up such that, on average, there is no significant measurable loss of graft length or width. Most of the allograft struts, 78%, maintained a radiodense appearance. Clinical results of femoral revision with strut allografting have shown satisfactory end results compared with historic controls, with an average Harris score of 79.6 and a 2.7% subsidence rate. Of particular note is that the subsidence rate and clinical scores did not vary with the state of the preoperative femur, as has been shown repeatedly in the past. The canine model shows that the strut allografts are biologically active. Through mobilization of mesenchymal tissue, they are transformed into vascularized calluslike structures while maintaining good strength, and then further remodel to lamellar bone.


Charnley low-friction arthroplasty in the young patient. One thousand three hundred forty-two Charnley low-friction arthroplasties (LFAs) were reviewed at an average of ten years four months after surgery. Patients' average age at surgery was 41 years. The clinical results at follow-up review remained excellent: 79% were pain free and 11% had no more than occasional discomfort. One hundred forty-one (10.5%) LFAs have been revised so far. Stem fracture has been completely eliminated. Revision for stem loosening has been reduced to below 1% and revision for socket loosening has also been reduced. The long-term problem remains socket wear--and with it--an increasing incidence of socket migration. Failure of component fixation is a short- and medium-term problem that has been improved by better component design and surgical technique.


A knowledge-based computer-aided design and manufacturing system for total hip replacement. A knowledge-based computer-aided design and manufacturing system (CAD-CAM) has been developed for total hip replacement. Knowledge-based refers to the fact that the design process is a computer program that has been provided with preprogrammed design rules. Compared with conventional CAD-CAM systems, the knowledge-based system is automated, requires less designer intervention, and increases the accuracy of the design process. The capabilities of the system make it ideal for the design of standard and custom total hip replacement. A full-fill, press-fit custom total hip replacement has been designed using the knowledge-based system. The early clinical results of a series of 37 replacements in 31 patients is described in this paper.


Development of a surgical robot for cementless total hip arthroplasty. The long-term success of cementless total hip arthroplasty (THA) may depend on bone ingrowth into the porous-fixation surfaces of the implant. The ingrowth process is facilitated when the surgeon achieves a satisfactory fit for the prosthesis. Clinically or roentgenographically visible failure and persistent thigh pain after cementless THA remain significant problems, both of which may be alleviated by more precise preparation of the femoral canal and selection of an appropriately sized prosthesis. The objective of this study was to obtain an exact fit for the prosthesis through the use of an image-directed surgical robot for femoral canal preparation.


Is it advantageous to strengthen the cement-metal interface and use a collar for cemented femoral components of total hip replacements? The mechanism of initiation of loosening of cemented femoral components is now known. It is debonding at the cement-metal interface. Current data strongly support the concept that a collar and improvement of the cement-metal interface are valuable. Precoating and having a roughened surface proximally and distally on the stem contribute to extended longevity of the cement-metal interface. Using contemporary instrumentation, collar-calcar contact can be achieved regularly and, once achieved, is well maintained for years.


The use of a collar and precoating on cemented femoral stems is unnecessary and detrimental. Evidence is presented, largely from clinical sources, that a large collar is not necessary for the transfer of load to the proximal femur in cemented total hip arthroplasty. In fact, the use of a collar may have a number of deleterious side effects that cannot be predicted from theoretical analyses. Concern is also raised over the use of precoated femoral stems.


Do we need to vacuum mix or centrifuge cement? In total hip surgery, the goal of porosity reduction techniques in the preparation of acrylic bone cement is to provide a stronger, more fatigue resistant material between the implant and bone. Conventional mixing of polymethylmethacrylate bone cement produces porosity of 5% to 16%, whereas vacuum mixing or centrifugation reduces the porosity to a range of 0.1% to 3.4%. Multiple studies have demonstrated that this results in a cement that has a significant increase in static and dynamic testing to failure. Fracture of the cement mantle has been found as a part of the failure pattern in many total hip prostheses requiring revision for loosening. Vacuum mixing or centrifugation produces a stronger cement to resist the component of loosening caused by fracture of the cement mantle. Where failure occurs at the bone-cement interface, as in cemented acetabular migration, no improvements from porosity reduction would be expected. Along with enhanced femoral designs, improvements in cement technique with modern methods of bone preparation and administration of the cement have resulted in a marked improvement in clinical and roentgenographic loosening rates in cemented femoral components at medium-term follow-up periods of five to ten years. Intact total hip prostheses, retrieved for reasons other than loosening, at longer-term follow-up periods, have shown intact bone-cement interfaces. However, these specimens have also shown incipient cracks in the acrylic cement that emanate from and connect defects in the cement mantle and at the metal-cement interface. The use of a void-free, structurally stronger material is expected to improve the stability and longevity of the cement supporting femoral implants.


Roentgenographic and mechanical performance of centrifuged cement in a simulated total hip arthroplasty model. Roentgenographic analysis showed that centrifugation significantly reduced the gross and regional porosity of the cement compared with hand-mixed controls in a simulated total hip arthroplasty model. Static failure test of the prosthetic system demonstrated that the centrifuged cement had significantly greater strength than the hand-mixed cement. Under low-cycle fatigue tests of the same composite models, there was a trend for the centrifuged cement to be stronger than the hand-mixed specimens, although statistically it was not significant. Thus, centrifugation can reduce porosity and significantly improve the static strength of cement in a simulated in vitro total hip replacement model. When cement is used, any possible improvement in the physical properties of bone cement should be considered.


Perivascular fibrosis of muscular pulmonary arteries in chronic obstructive pulmonary disease. We performed a morphometric analysis of peribronchiolar and perivascular fibrosis in lungs obtained at autopsy from six patients with chronic bronchitis, six with pulmonary emphysema, and four normal control subjects. The areas of fibrosis outside the smooth muscle layer of bronchioles and outside the external elastic lamina of muscular pulmonary arteries were measured and their thickness was then calculated by assuming a round airway or artery. Patients with chronic bronchitis had significantly thicker peribronchiolar fibrosis in bronchioles of 1 mm or less in diameter and also thicker perivascular fibrosis of the adjacent muscular pulmonary arteries than the other two groups. The extent of perivascular fibrosis was significantly correlated with peribronchiolar fibrosis only in the muscular pulmonary arteries adjacent to the bronchioles but not in those away from the bronchioles. These findings suggest direct extension of chronic inflammation from bronchioles to the adjacent muscular pulmonary arteries in chronic bronchitis but not in pulmonary emphysema. Such perivascular fibrosis might lead to sustained pulmonary hypertension.


Nasal CPAP continues to improve sleep-disordered breathing and daytime oxygenation over long-term follow-up of occlusive sleep apnea syndrome. To assess the effects of long-term nasal continuous positive airway pressure (CPAP) in occlusive sleep apnea syndrome (OSA), 17 patients with severe symptomatic OSA had repeated spirometry, arterial blood gases, and nocturnal polysomnograms off nasal CPAP after 3 to 46 months of treatment with nasal CPAP. Without loss of weight or change in respiratory mechanics, the ventilatory disturbance index fell from a mean of 87 events per hour to 57 events per hour (p < 0.0001), correlating with an improvement in mean nocturnal desaturation with sleep-disordered breathing events (r = 0.54, p = 0.03). Moreover, the daytime PaO2 rose significantly from a mean of 69 mm Hg to a mean of 82 mm Hg (P = 0.0001) at follow-up. The rise in daytime PaO2 was not only due to the alleviation of daytime hypercapnea observed in eight of nine hypercapneic subjects since the P(A-a)O2 gradient also decreased significantly. The improvement in PaO2 correlated significantly with the number of months of CPAP therapy, suggesting a continuing effect over time (r = 0.58, p = 0.015). These results indicate that there is a reversible element of the severity of OSA and suggest a result of nasal CPAP therapy may be to reverse the adverse and time-dependent effects of hypoxemia and sleep fragmentation on ventilatory control in severe OSA.


Sleep-disordered breathing in patients with Duchenne muscular dystrophy using negative pressure ventilators. We studied the occurrence of nocturnal disordered breathing events and O2 desaturations in 12 patients with late-stage Duchenne muscular dystrophy (DMD) using negative pressure ventilators. We also assessed the effects of O2 supplementation and nasal continuous positive airway pressure (CPAP) on disordered breathing events in selected patients and examined sleep quality in a small subgroup. Average age was 23 + 2 years and FVC was 293 + 33 ml. Eleven of the 12 patients had more than five disordered breathing events per hour during nocturnal monitoring, and the lowest O2 saturation was < 85 percent in nine patients. Nasal O2 (2 L/min) during negative pressure ventilation in four patients did not alter the frequency of disordered breathing events, prolonged the mean and maximum durations of events, and failed to eliminate severe O2 desaturations in two patients. Nasal CPAP was used in two patients during negative pressure ventilation and completely eliminated disordered breathing events in both. Overnight polysomnography during negative pressure ventilation in three patients demonstrated frequent awakenings that fell in frequency following elective tracheostomy in two patients and use of nasal CPAP in one. We conclude that negative pressure ventilation in patients with late-stage DMD is associated with frequent disordered breathing events and severe O2 desaturations in many patients. Concomitant use of O2 supplementation may prolong the events, but a switch to positive pressure ventilation or addition of nasal CPAP is effective therapy.


The relationship between sleep apnea syndrome and hypothyroidism. To evaluate the prevalence of obstructive sleep apnea syndrome (OSAS) in patients with hypothyroidism, the prevalence of hypothyroidism in patients with OSAS, the possible factors predisposing to sleep-related breathing disorder in hypothyroid patients, and the effect of thyroid hormone in treating hypothyroidism associated with OSAS, we studied 65 patients with proven OSAS (apnea index [AI] > 5) and 20 hypothyroid patients. All patients were monitored for one overnight sleep study using polysomnography (Grass 78). We found only two (3.1 percent) of 65 OSAS patients had thyroid hypofunction. Of 20 patients with hypothyroidism, two showed moderate to severe OSAS and three had mild OSAS. Patients with both hypothyroidism and OSAS had impaired respiratory drive, but this was corrected by thyroid hormone therapy. Patients with hypothyroidism without OSAS were younger and had a lower percentage of ideal body weight than those with both hypothyroidism and OSAS. All hypothyroid patients were snorers. Thyroid hormone replacement was effective in correcting snoring only after one year of therapy. We conclude the following: (1) an overnight sleep study is not necessary in every case of hypothyroidism; (2) thyroid function studies need not be done routinely for every OSAS patient; (3) thyroid hormone therapy is effective for OSAS but it takes longer to correct the snore than respiratory drive; and (4) age and body weight are related to the development of OSAS.


Chronic persistent cough and clearance of esophageal acid. Unexplained chronic persistent cough has been shown to be associated with increased episodes of otherwise asymptomatic gastroesophageal reflux; however, normal subjects without cough also exhibit some reflux. We postulate that the prompt clearance of refluxed acid from the esophagus may play an important role in the prevention of cough, and we sought to determine if patients with chronic cough have impaired clearance. Thirty patients with unexplained chronic cough underwent 24-h ambulatory esophageal pH monitoring. Compared to 12 matched control subjects, patients experienced significantly more episodes (all values expressed as median [range]) of reflux per 24 h (88.3 [5.0 to 338.0] vs 5.7 [0 to 13.0]; p < 0.0001) and had impaired clearance of esophageal acid as measured by the duration of individual reflux episodes (3.0 [0.1 to 20.5] min per reflux vs 0.7 [0 to 2.5] min per reflux; p < 0.01). We conclude that patients with chronic persistent cough have impaired clearance of esophageal acid.


Pattern of non-ICU inpatient supplemental oxygen utilization in a university hospital. Random assessments of SaO2 were performed via pulse oximetry in 274 hospitalized non-ICU patients prescribed supplemental O2 in a large tertiary care university hospital. In 507 assessments performed in patients inspiring the prescribed O2, 426 were receiving excessive amounts of O2 to maintain a SaO2 > or = 92 percent. In 233 of these assessments, SaO2 was > or = 92 percent while breathing ambient air. In an additional 193 assessments, the concentration of inspired supplemental O2 was excessive to maintain a SaO2 > or = 92 percent. However, in 81 assessments performed in patients inspiring O2, the prescribed amount was insufficient to maintain SaO2 > or = 92 percent. These results indicate that O2 prescription in hospitalized non-ICU patients is excessive or not required in the majority of cases. Furthermore, routine use of pulse oximetry in hospitalized patients prescribed O2 may be useful in determining the continued need for supplemental O2 and adjusting the proper concentration needed to avoid hypoxemia.


Acute outcome of directional coronary atherectomy vs standard balloon angioplasty in de novo left anterior descending stenoses. To assess the immediate outcome of directional coronary atherectomy (DCA) versus standard balloon angioplasty (PTCA) in de novo left anterior descending coronary stenoses, 25 consecutive atherectomies (22 men, 3 women) performed at The Toronto Hospital, between July 1990 and March 1991 were compared with 25 (14 men, 11 women) temporally matched successful angioplasties. Coronary stenoses were analyzed by quantitative arteriography, using the Coronary Measurement System (Leiden, The Netherlands), with estimation of transstenotic hemodynamics by fluid dynamic equations. Before and after procedure qualitative blood flow (TIMI criteria) was also evaluated, as was intimal haziness and coronary dissection. In comparison to PTCA, coronary atherectomy produced less residual minimum stenotic diameter (DCA, 2.75 +/- 0.55 vs PTCA, 1.70 +/- 0.44 mm, p < 0.001), and relative percent diameter stenosis (DCA, 17.9 +/- 10.7 vs PTCA, 34.4 +/- 10.7 percent, p < 0.001), with less transstenotic obstructive gradient (DCA, 0.2 +/- 0.2 vs PTCA, 1.0 +/- 1.5 mm Hg, p < 0.05), and greater estimated stenotic flow reserve (DCA, 4.86 +/- 0.15 vs PTCA, 4.50 +/- 0.48 x baseline, p < 0.05). Coronary atherectomy "normalized" TIMI flow patterns in virtually all patients (DCA, 2.96 +/- 0.20 vs PTCA, 2.72 +/- 0.45, p < 0.05), while creating less intimal haziness (DCA, 10/25 [40 percent] vs PTCA, 23/25 [92 percent], p < 0.01), and coronary dissection (DCA, 6/25 [24 percent] vs PTCA, 16/25 [64 percent], p < 0.05). Therefore, when compared with standard balloon angioplasty, DCA produces less residual stenosis, better transstenotic hemodynamics, while decreasing the frequency of coronary artery damage, in de novo left anterior descending stenoses.


Creatine kinase and creatine kinase-MB isoenzyme during and after exercise testing in normal and obese young people. We report creatine kinase (CK) and CK-MB values during a cycloergometric test up to maximal work capacity in 10 normal subjects aged 20 to 39 years (mean body mass index, 22 kg/m2) and 11 obese patients aged 17 to 42 years (mean body mass index, 41 kg/m2), all without any cardiorespiratory diseases. Total CK was significantly higher in obese patients. The CK-MB was not significantly different between the two groups, except at the first recovery when it was increased in obese patients and decreased in normal subjects. These results could be due to more important total stress of the total musculature, especially cardiac, and especially cardiac musculature in obese patients during a physical effort. Considering the mean values of total CK of our obese patients, it may be possible that they have myocardial damage at percentages of CK-MB less than those of lean subjects generally accepted at more than 4 percent. Moreover, in obese heart patients myocardial distress during exercise testing may be present despite heart rate at peak exercise beneath the theoretic maximal.


Using contrast material-enhanced echocardiography to identify abnormal pulmonary arteriovenous connections in patients with hypoxemia. The phenomenon of abnormal pulmonary arteriovenous connections in patients with acquired lung disease rarely has been reported. We report three patients with acquired lung disease and hypoxia that did not respond to the administration of 100 percent oxygen. Contrast-material-enhanced echocardiography demonstrated intrapulmonary right-to-left shunting in all three patients. These cases suggest that patients with hypoxia due to acquired lung disease may be screened by contrast-enhanced echocardiography to identify the presence and the location of anatomic right-to-left shunts.


Postoperative atelectasis reexpansion by selective insufflation through a balloon-tipped catheter. Although treatment of refractory atelectasis has been improved by pulmonary insufflation through FOB with balloon cuff, low pulmonary compliance and high critical opening pressure of alveoli in the atelectatic areas require a more selective approach to prevent pressure dispersion to highly compliant zones. To achieve the highest insufflation selectivity and reduce patient discomfort, we have devised a small caliber balloon-tipped catheter to easily reach even the minor branches of the bronchial tree. This result was obtained by utilizing the performed curve of the catheter distal end after withdrawing the internal stylet. The catheter was introduced through the nostrils (16 patients) or through an endotracheal tube (two patients) and advanced under fluoroscopic guidance. Reexpansion of atelectatic areas was accomplished by repeated air injections through a 60-ml syringe. No complications were observed. Complete disappearance of x-ray film evidence of atelectasis was obtained in 15 patients and partial reexpansion in 3 patients.


Can portable chest x-ray examination accurately diagnose lung consolidation after major abdominal surgery? A comparison with computed tomography scan. To prospectively quantify the degree of accuracy of portable chest x-ray film examination in the detection of postoperative lung consolidations. Nineteen patients had a chest x-ray film and computed tomography (CT) scan the day before and 48 h following elective abdominal aortic replacement. The diagnosis of lung consolidations by x-ray film examination showed sensitivity of between 0.33 and 1.00, depending on the lung zone considered (lower at the lung bases). Specificity always was greater than 0.79. Radiologic lung volume decreased 16 percent postoperatively (p < 0.01) on average and noninflated parenchyma increased by a factor of 3 (p < 0.0001). Postoperatively, PaO2 correlated with the amount of condensed lung by CT scan (p < 0.002). In postoperative conditions, x-ray film examination is a method which presents good specificity but poor sensitivity in the diagnosis of lung consolidations.


Lung cancer in patients with human immunodeficiency virus infection compared with historic control subjects. Lung cancer infrequently may be associated with human immunodeficiency virus (HIV) infection. This retrospective case-control study was undertaken to determine if there were differences in age, sex, and stage distribution and in survival between HIV-positive and HIV-indeterminate lung cancer patients. We compared 19 patients with both pathologically verified lung cancer and HIV infection proved by serologic study with lung cancer patients with an indeterminate HIV status. All 19 HIV-positive lung cancer patients were men. This was significantly (p = 0.004) different from the 69 percent male preponderance in 1,335 HIV-indeterminate lung cancer patients. Median ages of HIV-positive and HIV-indeterminate patients were 48 and 61 years, respectively. HIV-positive patients were significantly (p = 0.0139) younger. Stage distribution was similar in both groups. Histologic features and smoking were not significantly different between the two groups. Survival data that were available in 16 HIV-positive patients were compared with 32 HIV-indeterminate control subjects matched for stage, age, sex, and race. The median survival was three months in the HIV-positive group and ten months in the HIV-indeterminate cohort. The survival was significantly different (p = 0.002). There were no one-year survivors in HIV-positive lung cancer patients.


Increased inhaled bronchodilator vs increased inhaled corticosteroid in the control of moderate asthma. Undertreatment of chronic asthma may reflect uncertainty as to how it may be best controlled. We compared the effects of increased inhaled corticosteroid vs regular inhaled bronchodilator in 32 adult asthmatics. During three 16-week treatment periods, comprising baseline inhaled corticosteroid (mean 505 micrograms daily) and on-demand beta-agonist, baseline inhaled corticosteroid and increased (regularly scheduled four times daily) beta-agonist, and increased inhaled corticosteroid (mean 1478 micrograms daily) and on-demand beta-agonist, subjects recorded symptoms, morning and evening peak flow, and additional medication. Of 25 subjects whose control differed significantly between treatments with baseline vs increased corticosteroid, 22 (88 percent) favored the increased dosage (p < 0.001). Of 28 subjects whose control differed between treatments with regular beta-agonist vs increased corticosteroid, 24 (86 percent) were better controlled with increased inhaled corticosteroid and were worse with regular beta-agonist (p < 0.001). Only one quarter the number of exacerbations were experienced during treatment with increased inhaled corticosteroid. Upper airway adverse effects were minor and easily controlled. Hence, asthma with persistent symptoms was better controlled by increased inhaled corticosteroid therapy than by increased use of inhaled beta-agonist.


Skeletal muscle metabolism in the chronic fatigue syndrome. In vivo assessment by 31P nuclear magnetic resonance spectroscopy. Previous study of patients with chronic fatigue syndrome (CFS) has demonstrated a markedly reduced dynamic exercise capacity, not limited by cardiac performance and in the absence of clinical neuromuscular dysfunction, suggesting the possibility of a subclinical defect of skeletal muscle. The in vivo metabolism of the gastrocnemius muscles of 22 CFS patients and 21 normal control subjects was compared during rest, graded dynamic exercise to exhaustion and recovery, using 31P nuclear magnetic resonance (NMR) spectroscopy to reflect minute-to-minute intracellular high-energy phosphate metabolism. Duration of exercise was markedly shorter in the CFS patients (8.1 +/- 2.8 min) compared with the normal subjects (11.3 +/- 4.3 min) (p = 0.005). There were large changes in phosphocreatine (PCr), inorganic phosphate (Pi), and pH from rest to clinical fatigue in all subjects, reflecting the high intensity of the exercise. The temporal metabolic patterns were qualitatively similar in the CFS patients and normal subjects. There were early and continuous changes in PCr and Pi that peaked at the point of fatigue and rapidly reversed after exercise. In contrast, pH was relatively static in early exercise, not declining noticeably until 50 percent of total exercise duration was achieved, and reaching a nadir at 2 min postexercise, before rapidly reversing. There were no differences in pH at rest (7.08 +/- 0.04 vs 7.10 +/- 0.04), exhaustion (6.85 +/- 0.17 vs 6.76 +/- 0.17) or early (6.64 +/- 0.25 vs 6.56 +/- 0.24) or late recovery (7.09 +/- 0.04 vs 7.10 +/- 0.05), CFS patients vs normal subjects, respectively (NS). Neither were there intergroup differences (NS) in PCr or Pi. Although, quantitatively, the changes in PCr, Pi, and pH were marked and similar in both groups from rest to exhaustion, the changes all occurred much more rapidly in the CFS patients. Moreover, adenosine triphosphate (ATP) was significantly (p = 0.007) less at exhaustion in the CFS group. Patients with CFS and normal control subjects have similar skeletal muscle metabolic patterns during dynamic exercise and reach similar clinical and metabolic end points. However, CFS patients reach exhaustion much more rapidly than normal subjects, at which point they also have relatively reduced intracellular concentrations of ATP. These data suggest a defect of oxidative metabolism with a resultant acceleration of glycolysis in the working skeletal muscles of CFS patients. This metabolic defect may contribute to the reduced physical endurance of CFS patients. Its etiology is unknown. Whether CFS patients' overwhelming tiredness at rest has a similar metabolic pathophysiology or etiology also remains unknown.


Lung cancer in young adults.

Lung cancer in young adults. To define the basis for the conflicting reports on the prognosis of lung cancer in young adults. Retrospective review of lung cancer patients between 1977 and 1988. Medical centers in Chicago (Northwestern Memorial Hospital), northern Israel (Rambam Medical Center), and northern Italy (S. Anna and U. of Pavia Hospitals). Patients were < or = 45 years of age with a diagnosis of primary lung cancer identified from tumor registry records, pathology reports, and hospital charts, plus a sample of patients > 45 years of age. In Chicago, younger patients had a higher incidence of chest pain, fever, and neurologic symptoms at presentation than the older patients, and fewer were asymptomatic. They also had more lower lobe lesions on chest roentgenogram, a higher incidence of adenocarcinoma, more advanced disease, an increased likelihood of receiving chemotherapy, and reduced survival (p < 0.03). The poorer prognosis was due to more advanced disease at presentation. In Israel, younger patients more frequently presented with stage I disease than the older patients and they had a higher incidence of adenocarcinoma, an increased likelihood of receiving treatment especially surgery, and better survival (p < 0.02). There were no differences between the two age groups for symptoms, symptom duration, and chest roentgenogram findings. Compared with the younger patients in Chicago and Israel, those from northern Italy had more squamous cell cancers and fewer adenocarcinomas, more commonly presented with stage I or II disease, received radiation therapy less frequently, and were given supportive care more often. Survival was low and comparable to that reported from Chicago. Differences exist in the clinical characteristics, pathologic findings, and prognosis of younger and older patients with lung cancer from the same region and of younger patients from different regions. The difference in prognosis is related in part to the stage of disease at presentation and the ability to undergo resectional surgery.


Reduction of pulmonary surfactant in patients with human immunodeficiency virus infection and Pneumocystis carinii pneumonia. We assessed qualitative and quantitative differences in surfactant lipid composition of bronchoalveolar lavage (BAL) fluid in patients with acquired immune deficiency syndrome (AIDS) and Pneumocystis carinii (PC) pneumonia. Five normal volunteers and 27 patients with human immunodeficiency virus (HIV) infection underwent BAL for evaluation of possible pulmonary infection. Bronchoalveolar lavage studies in eight patients were negative for PC organisms, and 19 were positive. Pneumocystis carinii pneumonia was graded (mild vs moderate to severe) by initial alveolar-arterial oxygen gradient. Bronchoalveolar lavage fluid was centrifuged, the lipids were extracted from the supernatant, and total lipid profiles of dephosphorylated glycerolipids were analyzed as trimethylsilylether derivatives by high temperature gas-liquid chromatography. Phospholipase A2 levels were determined using a radiolabeled E coli membrane method. Compared to the normal volunteers (109 +/- 13 micrograms/5 ml) and the PC negative group (107 +/- 13 micrograms/5 ml), total BAL lipid was reduced for both the mild PC pneumonia group (73 +/- 10 micrograms/5 ml) and the moderate to severe PC pneumonia group (46 +/- 4 micrograms/5 ml). There was a parallel reduction of diacylglycerol lipids: normal volunteers, 52 +/- 7 micrograms/5 ml; PC negative, 52 +/- 9 micrograms/5 ml; mild PC pneumonia, 35 +/- 7 micrograms/5 ml; and moderate to severe PC pneumonia, 15 +/- 2 micrograms/5 ml. Phospholipase A2 activity in moderate to severe PC pneumonia was twice that of the PC negative patients, and 30 times that for normals. The data demonstrate a marked diminution in surfactant glycerophospholipid in patients with AIDS and PC pneumonia and suggest a potential role for surfactant abnormality in the pathophysiology of this disease.


Time course of pulmonary function before admission into ICU. A two-year retrospective study of COLD patients with hypercapnia. Changes in cardiopulmonary function were retrospectively evaluated back to two years before acute exacerbations requiring ICU admission in 16 COLD patients with chronic hypercapnic respiratory insufficiency (age: 61 +/- 6 years, group A). Fifteen hypercapnic COLD patients matched for age, sex, lung function, and blood gas values not requiring an ICU admission in a period of two years, served as control subjects (age: 66 +/- 7, group B). Periodic assessments of spirometry, arterial blood gas values, echocardiography, body weight, and red blood cell count performed in stable state were compared for differences between groups and changes over a period of two years. The results indicated that basal body weight, rate of deterioration over time in FEV1, VC, blood gas values, bicarbonates, and RVD may be related to the necessity of ICU admission in COLD patients with hypercapnic respiratory insufficiency.


Resuscitation from severe acute hypercapnia. Determinants of tolerance and survival. A 46-year-old man underwent cosmetic facial surgery under general anesthesia. He was ventilated by mask with an oxygen-enriched gas mixture for 4 to 6 h and monitored by pulse oximetry. Despite adequate arterial saturation (SaO2 > 90 percent) throughout the procedure, he remained in a deep coma after termination of anesthesia. Initial arterial blood gas analysis revealed a pH of 6.60 and a PaCO2 of 375 mm Hg. The patient was intubated and placed on mechanical ventilation. As his respiratory acidosis resolved, he regained consciousness quickly and recovered without any neurologic deficits. This case of record extreme hypercapnia and review of the literature demonstrates that survival is possible in acute severe respiratory acidosis as long as tissue anoxia and ischemia are prevented. We discuss the tissue effects of acute hypercapnia and newer aspects of the nature of intracellular pH regulation in critical tissues that afford considerable tolerance to acidosis. The dependence of these mechanisms upon active ion transport underscores the importance of adequate tissue oxygenation and perfusion.


Large pericardial effusions in the acquired immunodeficiency syndrome. The increasing importance of the acquired immunodeficiency syndrome (AIDS) as a cause of large, clinically significant pericardial effusions has not been well documented. To determine the frequency and characteristics of large AIDS-associated pericardial effusions, we reviewed the records of 50 consecutive patients undergoing pericardiocentesis between 1985 and 1990; AIDS was the most common underlying illness and was present in 14 patients (28 percent). The pericardial fluid was diagnostic in three (21 percent) of the 14 cases (one bacterial, one positive for acid-fast bacilli, and one lymphoma). Of the 11 patients with nondiagnostic fluid, one underwent a pericardial biopsy which revealed granuloma consistent with mycobacterial disease, four had active pulmonary tuberculosis (TB), and two responded clinically to anti-TB therapy. Thus, in 8 (57 percent) of the 14 patients with AIDS, there was either definitive or suggestive evidence of mycobacterial disease. We conclude that AIDS is now a common underlying illness associated with large pericardial effusions and that mycobacterial disease may frequently be the etiology.


The relationship of clinical findings to CT scan evidence of adrenal gland metastases in the staging of bronchogenic carcinoma. To determine whether, during the staging of newly diagnosed bronchogenic carcinoma, clinical indicators predict the presence or absence of adrenal metastases detected by computerized tomographic (CT) scans. Retrospective review of charts and roentgenograms. Academic medical center. Two hundred five consecutive patients diagnosed with bronchogenic carcinoma, of whom 173 had sufficient data available for analysis. Charts were reviewed for abnormalities in three clinical categories (signs, symptoms, and routine laboratory tests) and the presence of extrapulmonary tumor spread. The CT scans were reviewed for evidence of adrenal involvement by radiologists blinded to clinical findings. Thirty patients had abnormal adrenal glands on CT scan. In 26 the abnormality was believed to represent adrenal metastasis, whereas in four the CT findings were consistent with adrenal adenomas. The frequency of adrenal metastases varied with the number of positive, clinical findings (chi 2 = 105.4; p < 0.001). All 26 patients with adrenal metastases had at least one clinical abnormality, and 21 (81 percent had abnormalities in either two or all three clinical categories. In 40 patients without any clinical indicators of widespread disease, none had CT evidence of adrenal metastases. The presence of adrenal metastases also varied with the extent of coexistent disease (chi 2 = 111.82; p < 0.001). Eighty-one percent (21) of the patients with and 18 percent of those without adrenal metastases had both intrathoracic and extrathoracic involvement. Our findings indicate that adrenal metastases are found in patients with a large tumor burden who have clinical indicators of widespread disease. We found no evidence of adrenal metastases by CT in any patient with a normal clinical evaluation. We conclude that CT scans through the adrenal glands are unnecessary when staging newly diagnosed bronchogenic carcinoma if the findings from the initial clinical evaluation are normal.


Oscillatory mechanics of the respiratory system in neuromuscular disease. Respiratory impedance measurements by means of the technique of forced oscillations together with spirometry and measurements of maximal mouth pressures were performed in 27 patients with a variety of neuromuscular disorders to assess the value of adding respiratory impedance measurements in the evaluation of lung function in neuromuscular disease. Using the technique of forced oscillations, impedance measurements are easily performed in physically disabled persons, since they require little active cooperation and no forced respiratory maneuvers. Normal respiratory impedance characteristics were found, although resistance values were somewhat higher than those found in normal subjects, signifying the absence of airflow limitation. Spirometric values were markedly reduced, as were maximal mouth pressures. No significant correlations were found between the forced expiratory volumes in 1 s (FEV1) and the impedance data. A strong curvilinear relationship was observed between Pemax and the RV/TLC ratio and a strong correlation existed between FEV1 and Premax. It is concluded from our study that forced oscillometry is a useful tool for the assessment or exclusion of airflow obstruction in patients with neuromuscular disorders when plethysmography is difficult to perform and forced expiratory flow-volume data reflect muscle weakness rather than airflow limitation.


Efficacy of engineering controls in reducing occupational exposure to aerosolized pentamidine. Aerosolized pentamidine administration may pose potential risks to health care workers exposed to fugitive drug and to infectious respiratory pathogens (eg, tuberculosis) generated by pentamidine-induced cough. Classic infection control methods may be applied to this problem, although the effectiveness of these measures in mitigating environmental pentamidine exposure is unknown. Lack of data fully characterizing pentamidine's mechanism of action or potential mutagenicity, carcinogenicity, or teratogenicity raises concern and suggests worker exposed and environmental contamination be minimized. We report herein on the efficacy of an aerosol containment hood in containing fugitive pentamidine aerosol during administration.


Effect of inspiratory muscle fatigue on inspiratory muscle relaxation rates in healthy subjects. Simple methods to diagnose inspiratory muscle fatigue in the clinical setting would be of considerable benefit. Inspiratory muscle relaxation rates are known to slow following induction of fatigue. Inspiratory muscle relaxation rates have been measured following a short sharp inspiratory effort against an occluded airway (sniffmouth) or through the unoccluded nostrils (sniffnostrils). Relaxation rates in the absence of fatigue are faster when sniffs are performed through the unoccluded nostrils. While both methods have been shown to be capable of detecting inspiratory muscle fatigue, there may be quantitative or qualitative differences between the two techniques in their ability to detect fatigue similar to the differences observed in the fresh state. Accordingly, we measured relaxation rates with the two sniff techniques in five healthy naive male subjects before and after induction of fatigue. Inspiratory muscle fatigue was induced by threshold loading at 80 percent of Pesmax until the subjects were unable to generate the target pressure. For those trials in which sniffnostrils were performed, the maximum relaxation rate from the esophageal pressure curve (MRRes) was significantly decreased following induction of fatigue in nine of ten trials, while the exponential time constant (taues) was significantly increased in all ten trials. In contrast, for those trials in which sniffmouth were performed, the MRRes was significantly decreased following induction of fatigue in only six of ten trials. Similarly, taues was significantly increased following induction of fatigue in only six of ten trials. In addition, the magnitude of change in the MRR or tau following induction of fatigue was quantitatively greater with sniffnostrils compared with sniffmouth. Similar findings were obtained when relaxation rates were measured from the diaphragmatic pressure tracing. In conclusion, changes in relaxation rate following induction of fatigue were quantitatively greater and more consistently observed when sniffs were performed through the unoccluded nostrils rather than against an occluded airway.


Exercise testing, 6-min walk, and stair climb in the evaluation of patients at high risk for pulmonary resection. To evaluate three types of exercise testing in prediction of death or prolonged mechanical ventilation after lung resection in high-risk patients, 16 patients underwent evaluation prior to resection. Eleven patients (group 1) had minor or no complications (arrhythmia, atelectasis, pneumonia) and five patients (group 2) died within 90 days of surgery. Exercise testing showed that group 1 had a longer 6-min walk distance and a higher stair climb than group 2. The maximum oxygen uptake on a cycle ergometer was not significantly different between groups, although only ten patients completed this test. Group 1 had a significantly greater calculated oxygen uptake with stair climbing than group 2. A 6-min walk distance of greater than 1,000 feet and a stair climb of greater than 44 steps were predictive of successful surgical outcome. Preoperative exercise testing is a useful adjunct to traditional spirometric testing in evaluation of the high-risk surgical patients.


Venous hyperoxia after cardiac arrest. Characterization of a defect in systemic oxygen utilization. Supranormal mixed venous oxygen saturation (mixed venous hyperoxia), although reported, has never been characterized in humans resuscitated from cardiac arrest (postarrest cardiogenic shock). By contrast, cardiogenic shock without cardiopulmonary arrest (primary cardiogenic shock) is accompanied by mixed venous hypoxia under similar conditions of low oxygen delivery (DO2). The appearance of mixed venous hyperoxia indicates an excessive supply relative to demand in perfused tissue or cellular impairment of oxygen utilization, ie, low systemic oxygen consumption (VO2). Failure to improve VO2 has been associated with a poor outcome in other shock states. This study evaluates the clinical significance of mixed venous hyperoxia and its implications for impaired systemic oxygen utilization. The oxygen transport patterns in surviving and nonsurviving cardiac arrest patients are compared for their prognostic and therapeutic implications. Consecutive, nonrandomized series. Large urban emergency department (ED). Adult normothermic, nontraumatic out-of-hospital cardiac arrest patients presenting to the ED who develop a return of spontaneous circulation (ROSC). On arrival to the ED, a fiberoptic catheter was placed in the central venous position for continuous central venous oxygen saturation monitoring (ScvO2). A proximal aortic catheter was placed via the femoral artery for blood pressure monitoring. Upon ROSC, the fiberoptic catheter was advanced to the pulmonary artery. Mean arterial pressure (MAP), cardiac index (CI), VO2, DO2, systemic oxygen extraction ratio (OER), and systemic vascular resistance index (SVRI-dynes.s/cm5.m2) were measured immediately and every 30 min. The duration of cardiac arrest (DCA) in minutes and amount of epinephrine (milligrams) administered during ACLS was recorded. Twenty-three patients were entered into the study. Survivors (living more than 24 h) and nonsurvivors (living less than 24 h) were compared. These findings indicate an impairment of systemic oxygen utilization in postarrest cardiogenic shock patients. In spite of a lower DO2 than survivors, the OER in nonsurvivors remained lower than expected. Venous hyperoxia is a clinical manifestation of this derangement. Epinephrine dose may have a causal relationship. The inability to attain a VO2 of greater than 90 ml/min.m2 after the first 6 h of aggressive therapy was associated with a 100 percent mortality in 24 h.


Diagnostic value of hemosiderin-containing macrophages in bronchoalveolar lavage. Our objective was to determine if the hemosiderin content of BAL macrophages allows us to draw any differential diagnostic conclusions in a variety of lung diseases. One hundred one patients who underwent BAL for different diagnostic reasons were studied prospectively. The highest values for the hemosiderin score (HS) were found in patients with active alveolar hemorrhage and patients who had undergone heart transplantation for congestive heart failure. Compared to a control population, patients with Pneumocystis carinii pneumonia or invasive aspergillosis had a higher HS than patients with bacterial pneumonia or mycobacterial lung infection. High or intermediate values for HS were more often found in patients with a low than in those with a normal platelet count. The differential diagnostic conclusions which can be based on an HS are limited.


The effects of powered air supply to the respiratory protective device on respiration parameters during rest and exercise. The common chemical warfare protective masks impose an excessive respiratory load on the wearer due to elevated breathing resistance and increased dead space. For patients with severe respiratory disease, the excessive respiratory effort may be intolerable. Besides, the substantial negative pressure created within the mask during inspiration may result in an inward leakage in individuals having difficulties with proper facial fitting of the mask. The purpose of the current investigation was to evaluate the effects of a blower, actively driving air, through the mask's filter, at a flow (mean +/- SD) of 42 +/- 2 L/min, on respiratory parameters during rest and moderate exercise. Ten healthy subjects of either sex participated in two experimental sessions, wearing the mask with and without the blower. Each session included 6 min of sitting at rest and 6 min of walking on a treadmill (3.2 mph, and 10 percent grade). In nine of the subjects, the active air supply produced a positive inspiratory pressure at rest (5 +/- 4 vs -24 +/- 9 mm H2O peak inspiratory pressure with and without the blower, respectively, p < 0.0001). Inspiratory carbon dioxide concentration (FICO2) at rest was diminished (0.4 +/- 0.4 vs 1.3 +/- 0.7 percent with and without the blower, respectively; p < 0.01) while FIO2 increased from 19.5 +/- 0.7 percent to 20.6 +/- 0.4 percent with the device (p < 0.01). These changes were associated with a significant decrease in respiratory rate (15 +/- 2 vs 18 +/- 3 per minute, p < 0.01). During exercise the blower barely decreased the negative inspiratory pressures, had no effect on other respiratory parameters measured, but significantly shortened the inspiratory/cycle-length time ratio (0.46 +/- 0.03 vs 0.53 +/- 0.03, p < 0.005). The effects of active air supply were not different between male and female subjects. We conclude that the blower is expected to be a useful accessory to respiratory protective devices for patients with pulmonary disease.


Liquid phase characteristics of bronchoalveolar lavage in primary Sjögren's syndrome. We have previously reported that alveolitis correlates with clinical, roentgenologic, and functional parameters of pulmonary involvement in primary Sjögren's syndrome (1SS). In the present study, we analyzed the liquid phase characteristics of bronchoalveolar lavage (BAL) in the same 19 patients with 1SS. Our results show that patients with "high alveolitis" (group A, BAL lymphocytes > 15.2 percent) have increased values of total protein, albumin, IgA, and IgG and in their BAL fluid compared with patients with "low alveolitis" (group B) and control subjects. Also interleukin 2 (IL-2) was detected in more "high alveolitis" patients while IgM, IL-2R, and interferon gamma (IFN-gamma) were detected only in this group. There were no differences between the two groups in serum values of all above factors as well as in the presence of rheumatoid factor, extractable nuclear antibodies, and antinuclear antibodies. The increased values of immunoglobulins and cytokines in the BAL fluid of patients with intense alveolitis, in the absence of serum differences, speak for their local production and suggest activation of local immune mechanism.


Human pleural effusions are rich in matrix metalloproteinases. We identified and characterized type IV collagenase and gelatinase activity in pleural fluid from 32 patients. The capacity to substantially degrade type IV collagen was demonstrated in every pleural sample. Comparable results were also noted for the degradation of a radiolabeled gelatin substrate. Gelatin gel zymography of the pleural fluids revealed two prominent zones of lysis at 66 kDa and 92 kDa. These were identified by specific polyclonal antibodies as human matrix metalloproteinases MMP-2 and MMP-9. The concentration of MMP-2 in pleural fluid, as measured by enzyme-linked immunoassay, averaged 1,622 ng/ml whereas those of MMP-9 were 210 ng/ml. Substrate degradation activity was compared in both serum and pleural fluid from three patients and found to be similar. In serum this enzymatic activity was primarily due to MMP-9 whereas in pleural fluid, the predominant gelatinase was MMP-2. This was confirmed by immunoassay that showed that MMP-2 levels were two to five times higher in pleural fluid than in serum. We conclude that substantial amounts of MMP-2 and, to a lesser degree, MMP-9 are present in pleural effusions. The bioactivity and the immunoactivity of these enzymes did not help to distinguish among pleural fluids characterized as transudates, nonmalignant exudates, or malignant exudates. The differences in the distribution of these enzymes in pleural fluid and blood suggest that their presence is not due simply to the ultrafiltration of plasma, but rather to synthesis by the resident cells at the pleural surfaces.


Prospective comparative study of ofloxacin or ethambutol for the treatment of pulmonary tuberculosis. The efficacy of ofloxacin, rifampicin and isoniazid was prospectively compared with the regimen of ethambutol, rifampicin and isoniazid for the primary treatment of pulmonary tuberculosis in 124 patients. All drugs were given orally daily for nine months. Culture conversion rates three months after starting treatment were 98 percent in the ofloxacin group and 94 percent in the ethambutol group; by six months all patients in both groups were culture-negative. Significant radiological improvement of pulmonary infiltrates was observed in 83 percent of the ofloxacin group and 85 percent of the ethambutol group one year after starting treatment. No relapse in either group was observed during a two-year follow-up period after the cessation of chemotherapy. Ofloxacin appears to be as useful as ethambutol in the treatment of pulmonary tuberculosis when either drug is combined with isoniazid and rifampicin.


Diagnostic value of sialic acid in malignant pleural effusions. In this study, we measured pleural fluid and serum sialic acid levels in 70 consecutive patients hospitalized with pleural effusions and serum sialic acid concentrations in 20 healthy individuals chosen as control group. The cause of 26 pleural effusions was malignancy, and diseases other than malignant neoplasms were determined as the cause of 44 cases. Mean serum sialic acid levels in the patients with malignancies were higher than the levels in patients with nonmalignant diseases and the control group. Mean sialic acid level in the patients with nonmalignant diseases was increased compared with control group, but this increase was not as high as that in the patients with malignancies. In the patients with malignant neoplasms, mean pleural fluid sialic acid content was also higher than that found in other diseases. Sialic acid concentration of pleural fluid was correlated with serum concentration. However, pleural fluid to serum sialic acid ratio in malignant diseases was greater than that in the others. The specificity and sensitivity of pleural fluid sialic acid level in excess of 0.075 mg/ml in distinguishing malignant effusions were 68 percent and 77 percent, respectively. These values for pleural fluid/serum sialic acid ratio with the cut-off level of 0.7 were 55 percent and 65 percent. Our findings indicate that determination of sialic acid level in malignant pleural effusions has a diagnostic value.


Multisystem organ failure predicts mortality of ICU patients with acute respiratory failure secondary to AIDS-related PCP. To evaluate the ability of a variety of scoring systems to predict mortality of patients admitted to an intensive care unit (ICU) with acute respiratory failure (ARF) secondary to AIDS-related Pneumocystis carinii pneumonia (PCP). All patients with AIDS-related PCP admitted to ICU at St. Paul's Hospital between January 1, 1985 and April 1, 1991 were reviewed. For each case, the following scores were calculated from data obtained within 24 h of ICU admission: acute physiology and chronic health evaluation II (APACHE II); acute lung injury score; AIDS score as described by Justice and Feinstein; and modified multisystem organ failure (MSOF) score. The serum lactate dehydrogenase (LDH) level was also recorded when obtained within 24 h of ICU admission. A total of 52 ICU admissions in 51 patients were studied. Overall mortality was 65 percent. Mortality increased with increasing MSOF (p < 0.05) score and LDH (p < 0.05). Based on receiver operating characteristic (ROC) curves, the MSOF score and the LDH were found to be good predictors of mortality. Multivariate logistic regression showed that the MSOF score was the only independent predictor of mortality (p < 0.05). The AIDS score, APACHE II, and the acute lung injury score were not significantly associated with mortality. Addition of the serum LDH level improved the performance of both the MSOF and AIDS scores, though the AIDS score plus LDH performed no better than the LDH alone. Of all the scores tested, the MSOF plus LDH level was the best (p < 0.005) predictor of mortality. The modified MSOF score and the serum LDH level are the best predictors of mortality of patients admitted to ICU with ARF secondary to AIDS-related PCP. The performance of the MSOF score was enhanced when the LDH level was added. The AIDS score, APACHE II, and the acute lung injury score were not found to be useful in this group of critically ill patients.