Auto-MHC class II-reactive T cell line obtained from MRL/+ mice suffering from lpr-GVHD. II. Analyses of functional characteristics of T cell line by in vivo administration.

Functional characteristics of an autoreactive (I-Ek-restricted) T cell line (l/+ T1), previously established from MRL/M(p-)+/+(MRL/+) mice with lpr-GVHD, were analyzed in vivo. Intravenous injection of l/+ T1 cells to non-irradiated H-2k (MRL/+ or AKR) mice (but not H-2d mice) induced enhanced spontaneous proliferation of recipient spleen cells; this was also I-Ek self-restricted. This augmented self-reactivity seemed to be mediated by recipient L3T4+ T cells, since few l/+ T1 cells were detected in the spleen cells of l/+ T1-injected AKR mice by cell surface marker analyses, and the treatment of the spleen cells with anti-Thy-1.1 antibody (Ab) or anti-L3T4 Ab plus complement abolished this enhanced spontaneous proliferation. The production of IgM rheumatoid factor (RF) in AKR mice and IgG RF in MRL/+ mice increased, although no enhancement of anti-ssDNA Ab production was observed. Judging from both spleen B cell proportion and serum Ig levels, autoantibody induction by the injection of l/+ T1 cells was not associated with polyclonal B cell activation. When lethally irradiated B10 congenic mice were used as recipients, B10. BR mice showed elevated levels of IgM anti-ssDNA and IgM RF 1 wk after l/+ T1 cell injection; it is likely that lethal irradiation causes autoantigens, particularly DNA, to be exposed. These findings suggest that the autoreactivity of l/+ T1 cells can be transferred to recipient L3T4+ T cells via T-T interaction or the immunological network, and that increased autoreactivity induces autoantibody production in the presence of autoantigen stimulation. In contrast to the stimulatory effects observed in AKR and MRL/+ mice, MRL/Mp-lpr/lpr(MRL/lpr) mice showed a different response to the injection of l/+ T1 cells; spontaneous proliferation of spleen cells and autoantibody production were not enhanced, and suppression of the mitogen responses was observed. It is discussed that lpr-GVHD may be due to these unusual features of MRL/lpr mice.


Adjuvant arthritis pretreatment with type II collagen and Mycobacterium butyricum.

A treatment previous to adjuvant arthritis induction has been performed with type II collagen (CII) or Mycobacterium butyricum (Mb), which is the inducer of the pathology. Pretreatment was administered in two different ways: a) subcutaneously or intradermally 14 days before arthritis induction, and b) intravenously 3 days before induction. In order to relate the change in inflammation to the corresponding antigen immune response, serum antibodies and delayed type hypersensitivity (DTH) against CII or Mb were studied. Pretreatment with s.c. CII 14 days before induction produced slight protection against arthritis and significantly delayed its onset; systemic inflammation showed good positive correlation with anti-CII antibodies. The CII administered i.v. 3 days before arthritic challenge did not significantly modify the inflammatory process. The use of i.d. subarthritogenic doses of Mb 14 days before induction protected a high percentage of the animals from the posterior arthritic challenge; this protection was accompanied by high anti-Mb antibody titers and DTH reaction. When Mb was given i.v. 3 days before induction, a partial protection of inflammation was observed; arthritis was milder and its onset was delayed. These changes were accompanied by reduced humoral and cellular response to Mb.


Sensitization of allo-specific T lymphocytes in vivo: role of antigen-presenting cells.

The migratory behavior of antigen-presenting cells was investigated in vivo. Purified murine splenic dendritic cells and splenic and peritoneal macrophages were labelled and injected subcutaneously in the hind foot-pads of mice and monitored for seven days. In the first 24 h, a small quantity of label was recovered from popliteal but not inguinal lymph nodes with radioactive (111In-oxine and 3H-uridine) but not fluorescent (1,1'-dioctadecyl 3,3,3'3'-tetramethylindocarbocyanine perchlorate and fluorescein isothiocyanate) labelling of the antigen-presenting cells. Chemical fixation of the injected antigen-presenting cells had no effect on the detection of label in the popliteal lymph nodes, suggesting that it was unlikely to be due to active cellular migration. Label recovery from hind feet declined with time over the seven day period and was independent of the label type. Essentially the same observations were made whether the antigen-presenting cells were syngeneic or allogeneic to the injected mice and irrespective of the type of antigen-presenting cell used. However, allogeneic antigen-presenting cells, which did not migrate to the draining lymph nodes, successfully primed T lymphocytes in these lymph nodes as shown by a secondary in vitro mixed leukocyte reaction. Again, chemical fixation of the injected antigen-presenting cells had no effect on their ability to prime allogeneic T lymphocytes in the draining lymph nodes. These experiments suggest that, during experimental allo-sensitization via the subcutaneous route, indirect priming of allogeneic T lymphocytes may be a dominant pathway.


Immunosuppressive effects induced by the polysaccharide moiety of some bacterial lipopolysaccharides.

The immunomodulatory properties of several lipopolysaccharides (LPS) derived from clinical isolates of Pseudomonas aeruginosa, Branhamella catarrhalis, and Bordetella pertussis were evaluated for their capacity to influence the magnitude of the antibody response to type III pneumococcal polysaccharide (SSS-III), which is known to be regulated by suppressor and amplifier T cells (Ts and Ta, respectively). The administration of LPS, two days after immunization resulted in a significant increase in the antibody response. Such enhancement may be due mainly to the ability of the lipid A moiety of LPS to abolish the negative effects of activated Ts, thereby enabling Ta function to be more fully expressed; however, B cell mitogenicity of the LPS molecule also may be involved. By contrast, treatment with LPS at the time of immunization with SSS-III induces significant suppression of the SSS-III-specific antibody response; such suppression is not induced by LPS or lipid A derived from Escherichia coli and Salmonella minnesota, and is independent of the capacity of LPS to activate B cells polyclonally, an activity generally attributed to the lipid A fraction of LPS. Studies conducted with the LPS of P. aeruginosa indicated that the suppression induced is T cell dependent and mediated by the polysaccharide (PS) fraction of LPS; it appears to be due-at least in part-to the capacity of PS to expand or increase the size of the precursor pool of Ts, activated in response to SSS-III. The significance of these findings to the pathogenesis of certain gram-negative infections is discussed.


The influence of dietary fat on the interaction of lymphocytes with high endothelial venules.

The specific adherence of lymphocytes to high endothelial venules (HEV) represents the first step in the lymphocyte emigration from blood into most lymphoid tissues. The interaction of lymphocytes with HEV exhibits a remarkable organ specificity, which appears to be mediated by complementary receptors on both recirculating lymphocytes (homing receptors) and tissue-specific HEV (vascular addressins). The expression of homing receptors varies and depends on factors such as lymphocyte subtype, stage of activation and maturation. As these receptors are glycoproteins, which are anchored in the cell membrane, it can be envisaged that their position and function are determined by the overall composition of the cell membrane itself. In this study we investigated the significance of dietary fat concentration and saturation for the interaction between lymphocytes and HEV. In addition to these functional studies, the expression of homing receptors in combination with T and B cell markers were analyzed. Using immunohistochemistry the effect on the presence and characteristics of lymphocytes and HEV in situ was studied. Changes in the dietary fatty acid composition resulted in an altered ability of T and B cells to adhere to HEV, without affecting their binding preference. The changed adhesion patterns seemed to be associated with alterations in the expression of adhesion molecules, that are essential for the lymphocyte migration. The latter observation might in turn be explained by the observed modifications in the fatty acid composition of the lymphocytes. These results suggest a role for the fatty acid composition of the nutrition in the process of lymphocyte recirculation.


Enhancement of antigen-specific activation of CD8+ memory cytotoxic T cells by B cell-derived factors.

Purified CD8+ T cells from influenza A/WSN-immune BALB/c (H-2d) mice respond with the generation of secondary A/WSN-specific Tc cells in vitro when stimulated with a synthetic peptide (NPP) with a sequence derived from influenza A virus nucleoprotein with high affinity for Kd class I MHC molecules. The process of the conversion of NPP-Kd-responding Tc cell precursors into effector Tc cells in a population of CD8+ T cells occurs with no demonstrable requirements for accessory cells or their lymphokine products. The addition of culture supernatants from several mouse and human B cell lymphomas and LPS-activated normal mouse B cells to the culture of NPP-stimulated immune CD8+ T cells enhanced the induction of secondary Ag-specific Tc cells. None of the tested supernatants in the absence of Ag (NPP) induced cytolytic Tc cells, indicating that B cell-derived secretory factors can exert their activity only on Ag-exposed CD8+ T cells. The augmentatory effect of these supernatants on Ag-specific activation of memory CD8+ T cells was attributed to the synergism between B cell-derived factors and IL-2 which is produced endogenously in cultures of NPP-stimulated D8+ T cells. The possible role of B cell-derived helper factors is discussed.


Rat thymic epithelium positively selects mouse T cells with specificity for rat MHC class II antigens but fails to induce detectable tolerance in the mouse T cells to the rat MHC antigens.

BALB/c (H-2d) nude mice were grafted with allogeneic AKR/J (H-2k) or xenogeneic (ACI-N rat, RT1av1) fetal thymuses which were depleted of hemopoietic cells by incubating with 2'-deoxyguanosine (2'dGuo) in vitro prior to grafting. The nylon-wool-passed LN T cells from nude mice grafted with 2'dGuo-treated AKR/J thymus showed a poor proliferative response to B10BR (H-2k) stimulator cells, confirming that mouse thymic epithelium has the capacity to induce tolerance against the mouse MHC antigens on the thymic epithelium. On the other hand, the nylon-wool-passed LN T cells from nude mice grafted with untreated or 2'dGuo-treated ACI/N rat thymus showed significant proliferative responses to ACI/N, which can be blocked by anti-rat MHC class II mAb, whereas the nylon-wool-passed LN T cells from nude mice grafted with syngeneic thymus hardly responded to the xenogeneic stimulator cells. These results suggest that rat thymic stromal cells including thymic epithelium can not induce detectable tolerance in mouse T cells to rat MHC antigens; but rat thymic epithelium may positively select mouse T cells with specificity for rat MHC class II antigens, resulting in a mouse T cell repertoire with strong xeno-reactivity.


Cytokine production by murine cells activated by erythrogenic toxin type A superantigen of Streptococcus pyogenes.

The mode of pathogenic action of the Steptococcus pyogenes superantigen erythrogenic toxin type A (ETA) in causing toxic shock-like syndrome in humans is thought to be mediated by massive release of cytokines by patients immune cells. The cytokine-inducing capacity of ETA as an extracellular protein was compared with that of lipopolysaccharide (LPS), a component of cell wall of gram-negative bacteria. Peritoneal macrophages and splenocytes of BALB/c and C3H/HeJ mice were stimulated by ETA and LPS. Tumor necrosis factor (TNF), interleukin 3 (IL-3) and interleukin 6 (IL-6) activities in the supernatants of stimulated cells were evaluated. In contrast to LPS, ETA induced only low amounts of IL-6 and no detectable TNF activities in peritoneal macrophage supernatants. ETA-triggered BALB/c and C3H/HeJ splenocytes produced great amounts of IL-6. ETA triggered the production of IL-3 by both mice strains splenocytes in a dose dependent manner. The amounts of IL-3 in supernatants were comparable to those induced by concanavalin A. The simultaneous presence of ETA and LPS in macrophage and splenocyte cultures induced a slight enhancement above an additive value after 72-96 h. Challenge of BALB/c mice with ETA 6 h before the harvest of peritoneal macrophages led to an enhanced production of IL-6 upon stimulation with ETA as well as with LPS. Splenocytes of nude BALB/c mice did not produce IL-6 upon stimulation with ETA, whereas LPS-induced IL-6 production was similar in these mice and in their littermates. The pathogenic effect of ETA on host's immune cells could most likely be explained as a consequence of T cell activation. The results confirm also that LPS- and ETA-induced shock is mediated by different cell types.


Functional analyses of lpr gene in MRL/Mp-lpr/lpr mice. Role of lymph node stromal cells in lpr-lymphadenopathy.

To clarify the mechanism by which the lpr gene causes lymphadenopathy, we established an experimental system to induce lymph node (LN) swelling in unaffected mice. In MRL-(+)/+ mice that had been 5 Gy-irradiated and grafted with bone marrow cells (BMCs) plus LN from MRL-lpr/lpr mice, a remarkable enlargement of the LN grafts was seen. The enlarged grafts lacked normal LN structure and were indistinguishable from LNs of MRL-lpr/lpr mice. The induction of LN swelling by this method was achieved not only in [MRL-lpr/lpr-->MRL-(+)/+] but also in [MRL-lpr/lpr-->BALB/c], [MRL-lpr/lpr-->C3H], [B6-lpr/lpr-->B10.Thy1.1], and [B6-lpr/lpr-->BALB/c] combinations. Furthermore, the lpr/lpr LN grafts developed lymph node swelling even without the transplantation of BMCs. Most cells in the grafted LNs disappeared within a few days, and large clear fibroblast-like cells then became dominant for 1 to 4 weeks. Thereafter, lymphoid cells increased and had filled the graft by the 8th week. The LN grafts obtained from MRL-lpr/lpr (but not MRL-(+)/+) mice showed the ability to transfer LN node swelling into the secondary MRL-(+)/+ hosts two weeks after the primary transplantation. These results strongly suggest that the fibroblast-like LN stromal cells play a crucial role in lpr-associated lymphadenopathy.


Physical and sexual growth pattern of affluent Indian children from 5 to 18 years of age.

The present study was conducted to study growth parameters on 12,899 boys and 9,951 girls of affluent class from 8 States of the country. In pooled data, the 50th centile height approached 30-40th centile till 6 1/2 years in boys and up to 10 years in girls, and ultimately the height growth curves for both fell between the 10-20th centile of NCHS standards. Similarly, for weight, they approached 10-20th centile of NCHS at the age of 17 yr. Comparison with other European countries showed that Indian affluents are shorter and lighter; however, they are similar to their counterparts of Asian origin. The secular trend for height in Delhi showed increase of 2.1 cm for boys, and 2.7 cm for girls per decade at 17 yr and 14 yr, respectively. In Varanasi, the corresponding trend was 1.5 and 2.1 cm at 16 yr for boys and girls, respectively. The mean ages for genital development stages G 2-5 were 11.9, 13.3, 14.6 and 15.9 yr; respectively. In girls, the breast development Stages B 2-5 had mean ages of 10.9, 12.8, 13.9 and 14.8 yr, respectively. The mean age for menarche was 12.6 yr. In 14 yr old boys, the mean height may vary between 150.3, 155.8, 161.2 and 165.2 cm and mean weight between 38.0, 42.5, 46.8 and 52.9 kg for genital stages G 2-5, respectively. Similarly, girls of 12.5 yr (close to menarcheal age of 12.6 yr) had mean height 145.3, 150.3, 152.1 and 153.8 cm and mean weight 34.7, 41.2, 45.4 and 54.4 kg for breast stages B 2-5, respectively. It is recommended that for growth assessment during adolescence these charts in relation to sexual development and age be used for comparison.


Bacteremia and bacterial infections in highly febrile children without apparent focus.

To find the incidence of bacteremia and serious bacterial infections in febrile children without an apparent focus of infection, we prospectively studied 100 febrile children aged 1 month-3 years with a rectal temperature > or = 39 degrees C. Ten children had a blood culture positive bacteremia and nine had serology positive for bacteremia; 6 had urinary tract infection, 5 otitis media and 8 meningitis. A diagnosis of non bacterial illness was made in 62 patients. Staphylococcus aureus was the most common bacteriologic isolate on blood culture (five) and by serology (eight). TLC > or = 15,000/cu mm m-ESR > or = 25 mm and temperature > or = 39 degrees C had high specificity (95-100%) but low sensitivity for diagnosis of bacteremia.


Triage of war wounded: the experience of the International Committee of the Red Cross.

The hospitals of the International Committee of the Red Cross are often faced with situations in which the number of war wounded requiring surgical attention overwhelms the available facilities. Hospital organization, equipment and changes of attitude necessary for health professionals are considered with respect to triage. Practical aspects of assessment and categorization of the wounded are considered in the light of a large experience; relocation and reassessment of those who do not warrant immediate surgery benefit patients and hospital staff alike. The importance of adherence to an emergency plan and respect for the decisions of the person in charge of the triage are emphasized. The difficult and stressful nature of triage of war wounded should always be taken into account.


TRISS analysis of trauma care: a Yugoslav perspective.

The TRISS method has been claimed to be useful in the evaluation of trauma care. The aim of this study was to compare our data with Major Trauma Outcome Study (MTOS) results in North America, and to note differences and strive to improve care in our system. Data were collected from 163 consecutively admitted trauma patients to the Intensive Care Unit, Accident and Emergency Centre, Belgrade, Yugoslavia. Systolic blood pressure, respiration rate and Glasgow Coma Score were obtained on admission and the Abbreviated Injury Score was presented by anatomical area. Data were analysed on an Amstrad PCW computer, using a special non-commercial program. The calculated expected survival out of 163 cases was 131.7 and observed 111 patients. Distribution of severity of injury of the study population had a greater severity of injury than did the baseline. Thus, although the observed survival was less than expected, this is not conclusive evidence of worse care. This applies especially to the group of patients over 54 years of age who suffered blunt trauma, whose higher mortality (23 observed and 15.6 expected out of 50 patients) can be attributed to the ISS score being almost double that of the MTOS population of comparable age. Penetrating trauma patients, in spite of severe injuries, had better survival than predicted. The TRISS method, in spite of its limitations, proved a useful method of evaluating trauma care, and can be run on a small computer without the necessity for special staff.


The perioperative care of orthopaedic and trauma patients in a high-dependency unit: a 2-year prospective audit.

There is an increasing trend towards the establishment of high-dependency units in large hospitals since it is thought that they conveniently 'fill the gap' between the intensive care unit and the routine wards. This paper prospectively reviews the results of management of 205 orthopaedic and trauma patients who passed through such a unit over a 2-year period. The unit was shown to provide effective and safe care for a group of particularly high-risk patients for whom care on a routine ward at times would be insufficient and for whom care on an intensive care unit is unnecessarily expensive and occasionally unavailable. The high-dependency unit as described in this paper represents an efficient use of resources for this group of patients.


Justification for evacuating acute subdural haematomas in patients above the age of 75 years.

The author has reviewed the outcome of 27 patients aged 75 years and over who had an operation for acute traumatic subdural haematoma at Frenchay Hospital, Bristol, over a 10-year period. There were 15 men and 12 women with a mean age of 79.2 years. The outcome at 6 months was determined using the Glasgow Outcome Score. Of the patients, 15 per cent made a good recovery, 15 per cent a poor recovery and 70 per cent died. The influence of age, sex, mechanism of injury, preoperative Glasgow Coma Score (GCS), pupillary reactivity to light, skull and limb fractures, clinical course, CT scan appearance and timing of operation were analysed in relation to the outcome. The results showed that a preoperative GCS of 4 or less and unilateral pupillary dilatation and non-reactivity to light were not compatible with good survival in the very elderly patient with acute subdural haematoma. Under these circumstances, operation is not justified. The prognosis was worse in patients who were unconscious immediately after injury and with a CT scan showing a subdural haematoma and a haemorrhagic contusion which required urgent early intervention. The prognostic indicators present may prove useful in the selection of patients for active surgical intervention.


Internal fixation or arthroplasty for displaced subcapital fractures in the elderly?

A series of 200 patients aged over 69 years admitted to this hospital with a non-pathological displaced subcapital fracture of the femur, have been studied prospectively. Approximately one-half were treated by internal fixation and the remainder by a hemiarthroplasty, the method of treatment being dictated by the preference of the on-call consultant. This has enabled a comparison between the two groups. At 1 year from injury there was no significant difference in the mortality or function of the survivors. Internal fixation resulted in fewer postoperative complications, a shorter hospital stay and a reduced cost of treatment. The reoperation rate for internal fixation was three times that after hemiarthroplasty. Despite the problem of non-union, this study suggests that internal fixation is the treatment of choice for displaced subcapital fractures in the elderly.


The monofixator in the primary stabilization of femoral shaft fractures in multiply-injured patients.

In multiply-injured patients with femoral shaft fractures, evidence grows that a fast primary temporary stabilization device is preferable to a definitive method of stabilization by intramedullary nailing or plate osteosynthesis. Conversion to intramedullary nailing is performed later. During a 16-month period, we treated nine patients with 10 femoral shaft fractures in this way. There were two open fractures and six other fractures were associated with severe soft tissue damage. The overall function result is excellent and consolidation was reached after a relatively short time. The advantages are clear: a shorter operation time, earlier mobilization and rehabilitation, and fewer complications.


Long-term prognosis of displaced Colles' fracture: a 10-year prospective review.

In all, 85 per cent of Colles' fractures are clinically satisfactory after 10 years. Clinical results improve little after 3 months. Displaced intraarticular fracture, wrist deformity and algodystrophy are associated with an unsatisfactory outcome.


Does plaster immobilization predispose to pulmonary embolism?

Over a 5-year study period, 22 patients with isolated lower limb injuries who were immobilized in a plaster cast developed a pulmonary embolus. This information was not available from orthopaedic audit. Better cross-specialty accounting is required if complications that span different hospital specialties are to be fully elucidated. This problem was heightened by the number of emboli occurring while the patient was being treated as an outpatient.


Isolated sternal fracture: a benign injury?

Since seat belt legislation was introduced in this country in 1983, we have seen an increasing number of patients admitted to our unit for observation following seat belt related sternal fractures. In order to determine the value of routine admission of patients with isolated sternal fracture we have reviewed a series of 104 consecutive patients admitted between February 1983 and February 1990 with this injury. Of these, 90 were sustained in road accidents, 79 of which were as a consequence of seat belt use. The average age of these patients was 54.5 years (range 11-85 years) with an average duration of hospital stay of 2.9 nights. No serious complications were observed. These findings suggest that there may be no need to admit these patients solely for observation if their initial clinical condition is satisfactory and there are no abnormalities identified by an anteroposterior chest radiograph and electrocardiography.


Emergency laparotomy for abdominal trauma.

We have retrospectively reviewed our experience of 153 consecutive patients who underwent emergency laparotomy for suspected intraabdominal injury over a 10-year period. The commonest cause of injury was road traffic accidents (61 per cent), and the commonest indication for operation was signs of peritoneal irritation (35 per cent). Peritoneal lavage was performed in 62 patients (41 per cent). The liver was the organ most frequently injured (52 patients, 34 per cent) and 52 per cent of these patients died. Splenic injuries occurred in 46 patients (30 per cent). The negative laparotomy rate was 16 per cent. Forty-five patients died (29 per cent) and five of these had negative laparotomies. The Injury Severity Score (ISS) of all patients who died was > 16.


When should a synthetic casting material be used in preference to plaster-of-Paris? A cost analysis and guidance for casting departments.

An accurate cost analysis of the use of one of the new synthetic casting materials (Cellacast) compared with plaster-of-Paris (Gypsona) was undertaken over a 3-month period in the fracture clinic of Cardiff Royal Infirmary. The mean duration of usage before failure for synthetic forearm, scaphoid and below-knee casts was found to be approximately twice that of plaster casts. The use of synthetic casting materials was found to be cost-effective in situations where there was thought to be a high probability that structural failure of the cast would occur. Guidelines for the use of plaster-of-Paris and synthetic casting materials are presented.


Musculoskeletal injuries in the Afghan war.

Among the 1274 patients admitted to a Pakistan border hospital from 1985 to 1987, the distribution and outcome of musculoskeletal war injuries differed from those seen in other conflicts. Serious complications from injuries were found in approximately 50 per cent of patients, of which most were wound infections, chronic osteomyelitis, and restriction of joint motion. Guerrillas in the Afghan war had no access to acute medical treatment in the field. Many patients died before reaching the hospital, as reflected in the low proportion of paraxial injuries; very high complication rates were noted for all injuries. Although some complications, such as soft tissue infection and foreign body retention are not site specific, other complications such as contracture, non-union, loss of range of motion, and chronic osteomyelitis are highly related to the region injured. Early surgical management and evacuation of those with musculoskeletal war injuries can greatly improve the outcome from war trauma and reduce the subsequent disability. However, the increasing use of hand-held anti-aircraft missiles may prevent the rapid evacuation of the wounded in future conflicts, and may make the situation seen in Afghanistan more common.


The role of tissue pressure recording in forearm fractures in children.

During a 25-month period, 15 children with severe forearm fractures had signs and symptoms suggestive of an early compartment syndrome and underwent tissue pressure measurements. Of these, seven were found to have elevated intracompartmental pressures and had decompressive fasciotomies performed. The remaining eight patients had normal pressures and subsequently made uneventful recoveries. Tissue pressure recording is a useful adjunct to clinical diagnosis in suspicious cases of compartment syndrome, particularly in children.


Meniscal suture: a simple method.

A simple technique of meniscal suture is described. It avoids the main problem with most other outside-to-inside suture techniques, which is that knots either have to be left inside the joint or have to be pulled out through the meniscus. These knots often come undone or damage either the joint surface or meniscus. Essentially, a suture is inserted from outside to inside through the meniscus, using a cannulated needle. The end of this suture is then pulled back out through a separate hole in the meniscus, using a suture loop inserted with another cannulated needle. The two ends of the first suture are then tied together.


Unnecessary arthroscopies.

A review of the results of arthroscopies on patients taken from an 'open access' service waiting list has been carried out. One-third of all arthroscopies proved to be negative. Accuracy of clinical diagnosis was not related to the clinical grade of the examining doctor. The excess annual cost to the Northern Ireland Orthopaedic Service of unnecessary arthroscopies may have been of the order of 89,000 pounds.


Control of life-threatening haemorrhage from the neck: a new indication for balloon tamponade.

We report the use of a Foley catheter, placed through the wound, to provide balloon tamponade of major bleeding from the neck and supraclavicular fossae. In 10 consecutive explorations for exsanguinating injury in these regions balloon tamponade was used eight times, and was judged to be fully effective in four patients, partly effective in one, and ineffective in three patients.


Mechanical properties of the Pinless external fixator on human tibiae.

In the treatment of either acute severe open tibial fractures or their sequelae, a convenient external fixator is desirable. The conventional transosseous fixation with pins entering the medullary cavity is associated with problems such as pin loosening and pin track infection. Due to the bacterial contamination of the medullary space via the pin track the change of treatment from primary external fixation to secondary medullary nailing is an infection risk. In order to minimize these problems an external clamp fixator, the Pinless, was created. Medullary penetration is avoided by substitution of the conventional pins with clamps. The latter are inserted by hand (removable handles) and anchored only in the bone cortex. The medullary cavity stays intact. But is this clamp fixation stable enough for clinical use? On paired human cadaver tibiae, we compared the mechanical properties of the experimental Pinless, the conventional AO-tubular fixator and the Ultra-X fixator. Clamps differing in size (small/large) and material (steel/titanium) were used and compared to Schanz screws (steel, 5.0 mm diameter). We measured the stiffness of comparable configurations (1 or 2 bars) under axial compression, four-point-bending in two planes, and torsion. The pull-out force of the different clamps in relation to the bone diameter and number of rocking movements during insertion was also determined. The Pinless configurations with small clamps and 1 bar showed stiffness values as follows (as a percentage of the corresponding AO-tubular fixator): 42/36% (steel/titanium clamp) axial stiffness, 61/43% bending stiffness perpendicular to the reference plane, 78/79% bending stiffness parallel to the reference plane, and 90/95% torsional stiffness. The corresponding Ultra-X device was not as stiff as the Pinless. The use of two longitudinal rods increased the relative stiffness only under axial compression. The mean pull-out force on the proximal tibia was 1011 N for the small steel clamp, 717 N for the large steel clamp, 681 N for the small and 777 N for the large titanium clamp. At the lowest tibial diameter the values were reduced by 10 to 43%. The rocking movements doubled the pull-out force, e.g. there was a pull-out force for the large clamp of 600 N with five rocking movements compared to 310 N without. The Pinless was not as stiff as the conventional AO-tubular device but stiffer than the clinically used Ultra-X, especially in sagittal bending, the main load on a tibial fracture in the first weeks after trauma.(ABSTRACT TRUNCATED AT 400 WORDS)


Stable temporary traction substitute with the Pinless external fixator.

The stable traction substitute with a JBPF seems a very promising indication for pinless clamps, offering good patient comfort and easy care. The implantation of a JBPF is possible under the same conditions as for conventional calcaneal traction. Although the stability provided is less than for conventional external fixators, it is sufficient for a temporary traction device. The JBPF does not affect secondary ORIF.


Biomechanical evaluation of the Pinless external fixator.

In open fractures especially in those with severe soft tissue damage, fracture stabilisation is best achieved by using external fixators. There are some intrinsic complications which occur during classical external pin fixation. To overcome the problem of pin track infection and vascular damage from drilling, the Pinless external fixator was developed. It is based on the idea of a forceps with trocar points, which only penetrate the bone cortex superficially. The function of the device was tested in two mechanical trials and two in vitro tests in which one pinless clamp was put under a controlled load of 50 N, 150 cycles/day and studied over a 5 week period in sheep. The loads and time range of the experiment were chosen to simulate a temporary fracture stabilisation in a patient not bearing weight. The main question to be answered was whether the Pinless external fixator would be able to maintain stable fixation. Furthermore, it was to determine the changes at the trocar-to-bone interface. The clamp was found to maintain 72% of the initially applied clamping force after 5 weeks of in vivo application and it was found to be tight at removal. Some decrease of clamping force was found during the first 20 days and then the force tended to level off. There was no slippage nor did the clamp penetrate the cortex. There were no obvious signs of infection around the trocar-holes and in the bacterial tests no pathological cultures were grown. Histology revealed very localised bone reactions, the indentation caused by the trocar tips being only 1.2 mm deep. The study concludes, as far as could be ascertained from these tests, that it is safe to use pinless external fixation for temporary fracture fixation.


Realistic standards for quality assurance.

Standards are playing an increasingly important role in the field of quality assurance for dental and laboratory working conditions and performances. Evaluation, in terms of characteristics and importance, varies with the individual position and views of the respective institutions and authors but realistic standards are required to implement meaningful quality assurance measures.


The Periotest method.

The Periotest is a new instrument for the diagnosis of periodontal diseases. The 'Periotest value' depends to some extent on tooth mobility, but mainly on the damping characteristics of the periodontium. The Periotest measures the reaction to a reproducible impact applied to the tooth crown. The Periotest value is a biophysical parameter.


CPITN assessment of periodontal treatment needs in the population of Zagreb, Croatia.

The aim of this study was to assess the prevalence and required treatment of periodontal disease in Zagreb using the CPITN system. A total of 3176 subjects of both sexes, divided into reference age groups, was studied using the methods and standards recommended by the World Health Organization, the Community Periodontal Index of Treatment Needs (CPITN). A very high prevalence of periodontal disease in the population of Zagreb was recorded. Gingivitis was found in the entire population of school children and deep pockets were present even in those aged 20 years, the prevalence progressively rising with age. The need for oral hygiene instruction was recorded in almost all subjects examined, and the highest need for specialist periodontal treatment was registered in more than 56 per cent of the oldest subjects, over the age of 64. The data suggests the need for better organisation of preventive services and a more conscientious approach to treatment.


Dental health of children in an integrated urban development programme for destitute mothers with twins in Addis Ababa.

The Ethiopian Gemini Trust in Addis Ababa is a charitable organisation which cares for mothers who have delivered twins or triplets. A dental preventive programme for the disadvantaged children in the Trust was begun and this paper describes the first objective of the programme, the determination of the levels of dental disease. Caries, periodontal disease, malocclusion and enamel opacities were recorded.


Dental hygiene practice: international profile and future directions.

Results of an international survey on dental hygiene are reported. The survey was conducted in 1988 through the International Dental Hygienists' Federation as part of a project to establish and maintain an international database on the profession. Information was collected by mail from national dental hygienist associations, using a 40-item questionnaire developed for the purpose; preliminary tabulations were validated by the associations. Information is presented for 13 countries-Australia, Canada, Denmark, Italy, Japan, Korea, The Netherlands, Nigeria, Norway, Sweden, Switzerland, the United States and the United Kingdom. Characteristics include historical development, numbers and distribution, education, regulation, scope of practice, employment settings and conditions, professional organisation, and perceived oral health and professional issues. The profiles and issues are examined in the light of broader socio-economic, demographic, epidemiological, technological and policy-related trends and changes. Implications for future health and organisational planning are noted.


Structural variations in the crystal structures of two homologous DL-Leu and delta-Leu containing peptides.

The similar conformations and interaction modes of Ac-DL-Leu-NMe2 and Ac-delta-Leu-NMe2 molecules in the solid state allow the comparison of their geometrical parameters. The most evident variations are essentially restricted to the alpha, beta-unsaturated side-chain which adopts the Z-disposition. The dimensions of the peptide backbone are much less sensitive to alpha, beta-unsaturation, with a small shortening by 0.04 A and 0.02 A of the N--C alpha and C alpha--C' bonds, respectively, and an increase by 6 degrees of the N--C alpha--C' bond angle. The ethylenic and amide groups in the delta-Leu derivative are far from coplanarity, and a significant electronic conjugation of the pi-orbital is likely to be rejected.


Solid phase peptide synthesis on hydrophilic supports. Part II--Studies using Perloza beaded cellulose.

Beaded cellulose (Perloza) was modified with acrylonitrile followed by reduction with diborane to give a functionalised support containing aminopropyl groups. This spacer arm was then further extended with a glycolamido or an Fmoc-amino acid-4-oxymethylphenoxyacetyl moiety. A number of peptides, including the Merrifield test peptide leucyl-alanyl-glycyl-valine, leucine-enkephalin, Acyl Carrier Protein (65-74), angiotensin I and II, ACTH(4-11) and LHRH were synthesised on the aminopropyl beaded cellulose support using modified t-butyloxycarbonyl (Boc) or fluorenylmethoxycarbonyl (Fmoc) synthesis protocols. The peptides were cleaved from the support and further purified.


Design, construction and application of a fully automated equimolar peptide mixture synthesizer.

A fully automated peptide synthesizer has been constructed that is capable of the synthesis of equimolar peptide mixtures and the simultaneous synthesis of 36 individual peptides. The synthesizer was constructed from a workstation of our own design utilizing a Zymark robot arm. A Macintosh II computer coordinates the movements of the robotic arm, the switching of over 40 solenoid valves and the monitoring of sensors in the workstation. The robot hands are used to deliver solvents from pressurized spigot lines and to pipet amino acid solutions from reservoirs to an array of reaction vessels. Liquid dispensing, reagent mixing and solvent removal are controlled from a multifunction I/O board in the computer. The design features of the synthesizer are presented, as well as the characterization of multiple individual peptides, a simple mixture of 19 components, and a complex mixture of 15,625 components.


Synthesis and characterization of defensin NP-1.

Defensins are a group of small, cationic, antimicrobial proteins found in the cytoplasmic granules of neutrophils and macrophages of a variety of mammalian species. One such defensin, NP-1, isolated from rabbit neutrophils, has been shown to consist of 33 amino acids rich in arginine and cysteine residues. We have synthesized NP-1 on an Applied Biosystems Model 431A peptide synthesizer using FastMoc chemistry involving HBtu [2-1H-benzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate] activation for coupling amino acids. The linear peptide was folded by air oxidation to the biologically active form containing three disulfide bonds and purified by reverse phase chromatography. The amino acid sequence of the synthetic peptide was confirmed by Edman degradation. Molecular weight determination by plasma desorption mass spectroscopy (PDMS) gave a value of 3898.6, in agreement with the expected molecular weight of 3898. The biological activity of the synthetic peptide, as measured by its antifungal activity against several pathogenic fungi, was indistinguishable from that of the natural NP-1. Also, the CD spectrum was equivalent to that of natural NP-1, indicating conformational identity of the two species.


Solution conformation of endothelin and point mutants by nuclear magnetic resonance spectroscopy.

Two-dimensional NMR techniques were utilized to determine the secondary structural elements of endothelin-1 (ET-1), a potent vasoconstrictor peptide, and two of its point mutants, Met-7 to Ala-7 (ETM7A), and Asp-8 to Ala-8 (ETD8A) in acetic acid-d3/water solution. Sequence specific NMR assignments were determined for all three peptides, as well as chemical shifts and NOE connectivity patterns. The chemical shifts of ET-1 and ETM7A are identical (+/- 0.05 ppm) except for the site of substitution, whereas marked shift changes were detected between ET-1 and ETD8A. These chemical shift differences imply that the Asp-8 to Ala-8 mutation has induced a conformational change relative to the parent conformation. All three molecules show the same basic nuclear Overhauser effect (NOE) pattern, which suggests that the gross conformation of all three molecules is the same. Small changes in sequential NOE intensities and changes in medium-range NOE patterns indicate that there are subtle conformational differences between ET-1 and ETD8A.


Conformational investigation of alpha,beta-dehydropeptides. Part. IV. Beta-turn in saturated and alpha,beta-unsaturated peptides Ac-Pro-Xaa-NHCH3: NMR and IR studies.

Solution conformations of three series of model peptides, homochiral Ac-Pro-L-Xaa-NHCH3 and heterochiral Ac-Pro-D-Xaa-NHCH3 (Xaa = Val, Phe, Leu, Abu, Ala) as well as alpha,beta-unsaturated Ac-Pro-delta Xaa-NHCH3 [delta Xaa = delta Val, (Z)-delta Phe, (Z)-delta Leu, (Z)-delta Abu] were investigated in CDCl3 and CH2Cl2 by 1H-, 13C-NMR, and FTIR spectroscopy. NH stretching absorption spectra, solvent shifts delta delta for NH (Xaa) and NHCH3 on going from CDCl3 to (CD3)2SO, diagnostic interresidue proton NOEs, and trans-cis isomer ratios were examined. These studies performed showed the essential difference in conformational propensities between homochiral peptides (L-Xaa) on the one hand and heterochiral (D-Xaa) and alpha,beta-dehydropeptides (delta Xaa) on the other. Former compounds are conformationally flexible with an inverse gamma-bend, a beta-turn, and open forms in an equilibrium depending on the nature of the Xaa side chain. Conformational preferences of heterochiral and alpha,beta-dehydropeptides are very similar, with the type-II beta-turn as the dominating structure. There is no apparent correlation between conformational properties and the nature of the Xaa side chain within the two groups. The beta-turn formation propensity seems to be somewhat greater in alpha,beta-unsaturated than in heterochiral peptides, but an estimation of beta-folded conformers is risky.


HPLC and PDMS analysis of cleavage products aid in the design of small, stable ANP analogues.

The degradation of a prototypical small analogue of atrial natriuretic peptide (ANP) has been studied using HPLC and mass spectrometric techniques. These studies revealed that removal of the N-terminal amino acid was the primary catabolic event in vitro. Based on this information the N-terminus was remanufactured to provide a family of more stable analogues. Additional stabilization was provided through modification of the C-terminal tripeptide. Through dramatically more stable in vitro, these new analogues do not appear to have longer in vivo half-lives.


Hydrogen fluoride catalyzed migration of side chain protecting groups onto Fmoc during solid phase peptide synthesis. Characterization by CF-FAB analysis of carboxypeptidase digestions and NMR spectroscopy.

The solid-phase synthesis of the N alpha-Fmoc analog of protein kinase C substrate (PKCS, Lys-Arg-Ala-Lys-Ala-Lys-Thr-Thr-Lys-Lys-Arg) was characterized by low recovery from the resin and the concomitant appearance of four impurities. FAB-MS revealed molecular weights for two of these impurities that corresponded to the desired peptide plus Tos or Bzl. The other two were justified by invoking a CO2 elimination of the Clz protecting group to yield: 1) peptide plus 2-chlorobenzyl (ClBzl) and 2) peptide plus ClBzl and Tos. A CF-FAB analysis of carboxypeptidase digestions allowed observation of peptide cleavage down to an ion corresponding to lysine, Fmoc, and the corresponding protecting group(s). These data revealed that the impurities were not the result of incomplete deprotection but the result of migration of the protecting groups to the N-terminal end of the peptide. NMR experiments were subsequently performed and revealed the exact site of substitution: the meta positions of the N-terminal Fmoc. These impurities are presumed to arise by electrophilic aromatic substitution of the fluorene group during HF treatment. The desired Fmoc analog served as a convenient, albeit low-yielding, intermediate for purification of the highly charged PKCS by preparative self-displacement HPLC.


Mass balance strategy for protein sequencing. Application to a protein with an extended DNPNNP repeating motif.

The value of the mass balance strategy is illustrated in the sequence determination of S. aureus V8 protease. Capillary electrophoresis, electrospray mass spectrometry, and high performance tandem mass spectrometry are used as well as proteolysis and Edman degradation. The carboxy terminus is found to contain 17 irregularly repeating units of the triptych motifs NNP and DNP, which provide a challenge to any strategy involving mapping, sequencing, and overlapping of hydrolytic peptides.


Structure-toxicity relationships in the amatoxin series. Structural variations of side chain 3 and inhibition of RNA polymerase II.

The amatoxins, highly toxic components of death cap Amanita mushrooms, bind strongly to RNA polymerase II (or B) in cell nuclei thus preventing the transcription of DNAs to hn-RNAs (Pre-mRNAs), the precursors of messenger RNAs. Three of the binding sites of the bicyclic octapeptides have been identified: an isoleucine side chain in position 6, a trans-4-hydroxyl group at proline in position 2 and a hydroxylated L-isoleucine side chain in position 3. No information exists about the stereochemical conditions at the beta-C-atom (C-atom 3) of this side chain. We have now synthesized the diastereomeric S-deoxo-amaninamides (Fig. 1) containing, in position 3, L-allo-isoleucine (analog 1), (2S, 3R)-2-amino-4-hydroxy-3-methyl butyric acid (analog 2), the diastereomer (2S, 3S)-2-amino-4-hydroxy-3-methylbutyric acid (analog 3) and D-isoleucine (analog 4). In the last synthesis, besides the "normal" bicyclic octapeptide 4, an isomeric Iso-4 was formed. The affinities for Drosophila RNA polymerase II were 100 times weaker as compared to gamma-amanitin for 1, 10 times weaker for 2, 200 times weaker for 3, 100 times weaker for 4, and more than 1000 times weaker for Iso-4. The results point to the importance of a methyl group in (R)-configuration at the beta-C atom of side chain 3.


Studies on sensitivity to racemization of activated residues in couplings of N-benzyloxycarbonyldipeptides.

A series of 24 peptides Z-Gly-Xaa(R)-OH where Xaa = 15 different residues and R = H, NH2, tBu, Bzl, Trt, Mtr, and StBu were coupled with valine benzyl ester in dimethylformamide or dichloromethane at +5 degrees. The accompanying racemization was determined by analysis of the epimeric products by normal phase high-performance liquid chromatography (HPLC) for Xaa(R) = Met, Cys(StBu) and Lys(Z) and by reversed-phase HPLC after removal of benzyl-based protecting groups for Xaa(R) = Ser(tBu), Thr(tBu) and Arg(Mtr). The coupling methods examined included mixed anhydride (MxAn) at -5 degrees, and N,N'-dicyclohexylcarbodiimide (DCC), benzotriazol-1-yl-tris(dimethylamino)phosphonium hexafluorophosphate (BOP) and O-benzotriazol-1-yl-N,N,N',N'-tetramethyluroniumhexafluorophosp hate (HBTU) in the presence of 1-hydroxybenzotriazole (HOBt). Very few couplings gave stereochemically pure products. The order of sensitivity to racemization of residues depended on the method of coupling and the solvent. It varied most when comparing MxAn to HOBt-assisted reactions; it varied moderately when comparing HOBt-assisted reactions. There was less variation in comparing BOP and HBTU reactions that are initiated by the same mechanism. Leu, Nle, Phe, Asn, Lys(Z) and Asp(OBzl) are identified as the residues least sensitive to racemization. DCC-HOBt generally led to less epimerization than the other methods.


Site-specific biotinylation. A novel approach and its application to endothelin-1 analogs and PTH-analog.

We have developed an expeditious method for the incorporation of the biotinylaminocaproyl moiety on the epsilon-amino group of a lysine residue within a peptide chain in a site-specific manner. Using t-Boc chemistry for the solid phase synthesis approach and a base labile, acid stable protecting group (Fmoc-) for the epsilon-amino group of the target lysine, we prepared fully protected resin bound peptides which are site-specifically biotinylated. Following HF cleavage, the uniquely biotinylated peptides were obtained in a high degree of purity. Using this approach, a number of biotinylaminocaproyllysyl derivatives of a monocyclic Endothelin-1 analog were prepared. Synthesis of selected bicyclic analogs of high affinity monocycles led to the preparation of the bicyclic [Nle7]ET-1 analog containing epsilon-biotinylaminocaproyllysine at position-9. This peptide, with Kd = 0.08 nM, has 1000-fold higher affinity for the ETA receptor than the commercially available N alpha-biotinylated Endothelin-1. The general utility of this biotinylation methodology was demonstrated by the synthesis of a site-specifically biotinylated PTH analog which contained several side chain functionalized amino acid residues in its sequence. The synthetic method reported here is convergent in that it allows the facile variation of the length of the spacer and also offers the potential to introduce in a site specific manner other groups such as affinity labels and fluorescent tags.


Isolation and primary structure of a potent toxin from the venom of the scorpion Centruroides sculpturatus Ewing.

A potent toxin has been purified from the venom of the scorpion Centruroides sculpturatus Ewing using the ion-exchange resin CM-Sepharose CL-6B at basic pH. The toxin, designated CsE M1, comprised 65 amino acid residues and its primary structure was established as: Lys-Glu-Gly-Tyr-Leu-Val-Asn-Ser-Tyr-Thr10-Gly-Cys-Lys-Tyr-Glu-Cys- Leu-Lys-Leu- Gly20-Asp-Asn-Asp-Tyr-Cys-Leu-Arg-Glu-Cys-Arg30-Gln-Gln-Tyr- Gly-Lys-Ser-Gly-Gly - Tyr-Cys40-Tyr-Ala-Phe-Ala-Cys-Trp-Cys-Thr-His-Leu50-Tyr-Glu- Gln-Ala-Val-Val-Trp - Pro-Leu-Pro60-Asn-Lys-Thr-Cys-Asn. CsE M1 is the most lethal protein to be identified in C. sculpturatus venom and the LD50 of the toxin, determined by subcutaneous injection into Swiss mice, is 87 micrograms/kg. CsE M1 shows strong structural similarity (92% positional identity) to the most potent beta-toxin, Css II, from the Mexican scorpion, Centruroides suffusus suffusus but is quite dissimilar to the previously characterized toxins with low potency isolated from C. sculpturatus Ewing.


Leishmania major: bacterial contamination of cutaneous lesions in experimental animals.

No bacterial contamination has been demonstrated in cutaneous leishmaniasis (CL) nodule and in lesions caused by Leishmania major in Balb/c mice up to 20 days after infection. However, although many phagocytic cells (polymorphonuclear leukocytes and macrophages) were present in the CL lesion, 80% of the lesions showed bacterial contamination that developed within the first 70 days of infection. Topical treatment of the lesion with an ointment containing 15% paromomycin and 12% methylbenzethonium chloride in soft white paraffin for 20 days eliminated all the Leishmania parasites and several of the associated bacteria including: Proteus vulgaris, Pasteurella multocida, Staphylococcus albus and Staphylococcus aureus. This treatment did not affect Escherichia coli, Klebsiella spp. and Pseudomonas aeruginosa. Total elimination of these bacteria was achieved only during the healing process, and within 20 days following termination of treatment. The rate of disappearance of bacteria inoculated alone into the base of the tail of normal uninfected Balb/c mice was much faster than that of bacteria inoculated into either the CL nodule or the CL lesion. This study suggests the development of local immunosuppression in the CL lesion that may be mediated by the Leishmania parasites and their metabolites.


Doppler measurement of left ventricular isovolumic intervals: a study of feasibility and correlation with conventional techniques.

Pulsed Doppler echocardiography allows simultaneous recording of left ventricular inflow and outflow blood velocities obtained from the apical 5-chamber view. In this study the feasibility and accuracy of pulsed Doppler measurements of left ventricular isovolumic relaxation and contraction times were compared with those derived from two conventional techniques that combined phonocardiograms and M-mode echograms (phono-echo) and M-mode echograms and electrocardiograms (ECG-echo). Thirty-seven subjects--24 healthy volunteers and 13 cardiac patients--were examined. Isovolumic relaxation was consistently longer than isovolumic contraction time. Younger age was associated with shorter isovolumic intervals, while heart rate had a negative correlation with these parameters (r = -0.5). Pulsed Doppler measurements of isovolumic relaxation correlated well with phono-echo, r = 0.89, and ECG-echo, r = 0.75. Isovolumic contraction times measured by Doppler correlated better with those derived by phono-echo, r = 0.75, than those by ECG-echo, r = 0.4. Better correlations were found for both measurements in the normal subgroup than in the whole group. Difficulty was encountered in measuring isovolumic contraction time by Doppler and ECG-echo in the absence of presystolic A-wave, and in subjects with varying cardiac cycle lengths. Thus, pulsed Doppler measurements of left ventricular isovolumic relaxation times were feasible and consistent with the other methods, while isovolumic contraction intervals by Doppler were not.


Colorectal cancer in patients over 70 years old. A prospective study of operative results.

All patients (284, mean age 70.8 years) admitted with a diagnosis of primary colorectal cancer to our surgical department during the years 1984-87 were evaluated prospectively. We compare 170 (59.9%) patients > 70 years old and 114 (40.1%) patients < or = 70 years. The overall operability rate was 97.3% and the resectability rate 92.8%. The overall operative mortality rate was 2.1%, four patients in the older group and two patients in the younger group (NS). Among patients who underwent emergency surgery, the operative mortality was 6.1% (4 patients). The overall morbidity rate was 26.7% without significant differences between the two age-groups. A separate subset analysis was done to compare the very old patients (age > or = 80) to the old patients (age 70-79). There were no significant differences between these groups in tumor location, presentation and staging, as well as in operability rate and operative morbidity and mortality. The operative mortality in those over the age of 80 was 3.5%. We concluded that age should not be a determinant in consideration of operation for primary colorectal cancer, since operative mortality and morbidity are similar in both the elderly and their younger counterparts.


Confusion as the presenting manifestation of vertebral osteomyelitis: a case report.

A 44-year-old patient presented with increasing confusion. He was first diagnosed as having intermittent pressure hydrocephalus but a further evaluation showed CSF pleocytosis and hypoglycorrhachia. Five weeks later, his physical examination was unrevealing. Nuclear imaging techniques were conflicting, with negative gallium- and indium-labelled white blood cells scans but a Tc scan pointing towards a vertebral infection. A well-demarcated lesion in the T9 vertebral body, demonstrated by CT scan, confirmed the diagnosis of vertebral osteomyelitis. Although we were unable to recover the causative organism, antibiotic treatment for presumed staphylococcal osteomyelitis resulted in full recovery. This case indicates that vertebral osteomyelitis may cause significant meningeal inflammation even in the absence of epidural or subdural abscess. We recommend that in patients with meningitis without a clear etiology vertebral osteomyelitis should be considered and pursued with CT scannings of the vertebrae, a procedure that can yield positive findings even when other scanning modalities are negative.


Standardized mortality ratios for Israel, 1983-86.

Standardized mortality ratios (SMRs), standardized by age, sex, continent of birth, and religion are presented by cause and region for the period 1983-86. Regional SMRs ranged from 90.6 in Jerusalem to 107.6 in Ramla. These differences may be due to direct and indirect occupational, environmental and socioeconomic effects as well as to possible health service differences. SMRs can be used to indicate regions where further in-depth epidemiological investigations are called for in order to ascertain the reasons for elevated disease specific SMRs. In addition, SMRs could be used as a global measure of all effects in order to adjust any regional budgetary allocation formula, based on capitation.


Investigation of suitability of devascularized upper half of the whole stomach as replacement for the esophagus.

One hundred and fifteen patients with esophageal cancer underwent esophageal replacement with the stomach. The patients were divided into group A (52 patients, stomach tube, ante- or retro-sternal route) and group B (54 patients, devascularized upper half of the whole stomach, posterior mediastinal route). The post-operative complications, post operative symptoms and nutritional status were investigated in both groups. Lung complications tended to occur more frequently in group A (28.8% versus 22.2%), showing no significant difference. The incidence of other complications did not show a remarkable difference between either group except for leakage at the site of anastomosis. Major leakage occurred in 11.5% and 5.6%, and minor leakage in 30.8% and 18.5%, respectively. Postprandial fullness, nausea, heart burn and diarrhea were found to be somewhat higher in Group B. Change of oral intake, body weight and other indices of nutritional status were investigated and compared with pre- operative data. The amount of oral intake and levels of serum albumin was higher in group B than in group A between one and 12 months. These results demonstrate the superiority of the devascularized upper half of the whole stomach as an esophageal substitute.


Comparative study of cerebral protection during surgery of thoracic aortic aneurysm.

During the past 5 years, 30 cases of thoracic aortic aneurysm were treated. Selective cerebral perfusion (SCP) and retrograde cerebral perfusion (RCP) were conducted for cerebral protection during aortic cross clamping. SCP was carried out in 5 cases of dissecting aneurysm (all Stanford type A, including a case of AAE) and 3 cases of arch aneurysm. RCP was conducted in 5 cases of dissecting aneurysm (4 Stanford type A, 1 Stanford type B with retrograde dissection) and 2 cases of aortic arch aneurysm. The mean cerebral perfusion time of SCP exceeded that of RCP (89 +/- 26 min in SCP versus 61 +/- 33 min in RCP p < 0.05). The hospital mortality rate was 38% (SCP) and 29% (RCP). Neurological complications were prolonged unconsciousness (1/8 in SCP, 1/7 in RCP) and transient paralysis (0/8 in SCP, 1/7 in RCP). Although the mechanism for the cerebral protective effect of RCP is unknown, this perfusion method is easy and safe, requiring little time for ascending and/or arch aortic reconstruction.


Ovarian sex cord tumor with annular tubules--a case report and review of the literature in Japanese.

A case of ovarian sex cord tumor with annular tubules (SCTAT) in a 41-year-old female is reported. The patient's chief complaint was menstrual irregularity, but the serum values of estradiol and testosterone were not elevated. On gross examination, the left ovary measured 8 x 7 x 6 cm in size and its cut surface was yellowish gray or yellow and solid with no cystic area. Histologically, the tumor was composed of simple and complex annular tubules, lined by columnar cells containing abundant lipid droplets. Eosinophilic materials in the center of the annular tubules were continuous with the basement membrane in the periphery, and showed immunoreactivity for type IV collagen. Also, hollow tubules, consisting of columnar cells with a truncated luminal surface and elongated trabeculae, composed of columnar cells with clear cytoplasm, were noted. These structures were reminiscent of Sertoli cell tumor. Based on these histological observations, it appears that SCTAT is a sex cord/stromal tumor made up of cells with differentiation in the direction of Sertoli cells rather than granulosa cells.


Laparoscopic cholecystectomy report of 30 cases.

Laparoscopic cholecystectomy (LSC) was attempted in 30 patients and was accomplished in 29 during the nine months between March and November 1991. Twenty eight patients had cholelithiasis with or without adenomyosis, and two had adenomyosis of the gall-bladder. Mean operative time was 219 min and postoperative pain was slight. Two complications (6.9%), including necrosis of the common hepatic duct and subcutaneous emphysema, were encountered. Patients with subacute and severe chronic cholecystitis were included in the cases. Thus this technique is recommended for almost all patients who require the removal of the gall-bladder for benign diseases.


Functional deficiency of antigen-presenting cells in the synovial fluid of rheumatoid arthritis.

In our study of rheumatoid arthritis (RA) patients, we observed a decrease of tetanus toxoid antigen-presenting capacity of synovial fluid (SF) adherent cells to autologous T cells of either SF or peripheral blood. Additionally, we found a higher capacity of adherent synovial cells to stimulate autologous T-lymphocytes. Our results suggest that antigen-presenting cells of the SF of RA patients have defects that may play a role in defective presentation of antigens in joints and may account for other abnormal functions important in the pathogenesis of RA.


HLAs and genes in Japanese patients with multiple sclerosis: evidence for increased frequencies of HLA-Cw3, HLA-DR2, and HLA-DQB1*0602.

The distribution of HLA-A, B, C, DR and DRB1, DQB1, DPB1 alleles was studied in 60 Japanese patients with clinically definite multiple sclerosis (MS) using serologic and genomic analysis. We found significant associations with HLA-Cw3 (p = 0.002, pc = 0.012, RR = 3.2), DR2 (p = 0.007, RR = 2.6), and DQB1*0602 (p = 0.04, RR = 4.0) in Japanese patients for the first time. The combined presence of Cw3 and DR2 gave a higher risk than each antigen alone. The reported increase in the frequency of DPw4 in Japanese MS patients [12] could not be confirmed by our genomic study. The frequencies of all of the residues in each variable region of the amino acid sequences of DQ beta and DP beta chains were not different between the MS patients and the controls. These results suggest that MS susceptibility may result from polygenic influences and from the presence of environmental factors.


Signal transduction by HLA class II molecules in human T cells: induction of LFA-1-dependent and independent adhesion.

Crosslinking HLA-DR molecules by monoclonal antibodies (moAbs) induces protein tyrosine phosphorylation and results in a secondary elevation of free cytoplasmic calcium concentrations in activated human T cells. Binding of bacterial superantigens or moAbs to DR molecules on activated T cells was recently reported to induce homotypic aggregation through activation of protein kinase C (PKC) and mediated by CD11a/CD54 (LFA-1/CAM-1) adhesion molecules. Here, we report that moAbs directed against framework DR, but neither DR1, 2- and DRw52- nor DQ- and DP-specific moABs induced homotypic aggregation of antigen- and alloantigen-activated T cells, antigen-specific CD4+ T-cell lines, a CD8+ T-cytotoxic cell line, and T-leukemia cells (HUT78). Protein tyrosine kinase (PTK) inhibitor herbimycin A partly blocked class-II-induced aggregation responses. In contrast, phorbol ester (PMA)-induced aggregation was essentially unaffected. A potent inhibitor of PKC, staurosporin, inhibited both moAb- and PMA-induced aggregation responses. The aggregation responses were completely inhibited by low temperatures, cytochalasins B and E, and partly inhibited by EDTA and CD18 moAbs, but unaffected by aphidicolin, mitomycin C, an adenylate cyclase inhibitor (2'5'-dideoxyadenosine), and moAbs against other adhesion molecules (CD2/CD58 [LFA-3], CD28/CD28 ligand B7, CD4, and CD44). In conclusion, HLA class-II-induced aggregation responses in activated T cells appear to involve PTK and PKC activation and to be mediated through CD11a-dependent and independent adhesion pathways.


Determination of cytotoxic T-lymphocyte precursor frequencies using europium labeling as a nonradioactive alternative to labeling with chromium-51.

We report on the use of europium (Eu) as a suitable nonradioactive alternative for target cell labeling in limiting dilution analysis (LDA) assays set up to determine cytotoxic T-lymphocyte precursor (CTLp) frequencies. A nonradioactive alternative to the commonly used chromium-51 (51Cr) release assay seems desirable because working with radioisotopes has some major disadvantages concerning possible health risks, environmental load, costs of facilities necessary for working with radioisotopes, and shelf life. Some groups have successfully applied the Eu release assay based on detection by time-resolved fluorometry, to tests in which NK- or LAK-cell activity or cytotoxic T-lymphocyte reactions were measured. This led to the investigation whether this method could also be applicable to the more specific determination of CTLp frequencies in LDA assays. After optimal labeling conditions had been established, the sensitivity of the Eu release assay was determined by performing several LDA assays in which the target cells were labeled with either Eu or radioactive 51Cr. When CTLp frequencies were compared, it was shown that the Eu release assay is at least as sensitive and specific as the 51Cr release assay. Moreover, although the labeling procedure takes longer, sample processing is much faster: only 1 second per sample. The fact that the Eu release assay is not radioactive enables the assay to be performed at any laboratory and even--because the frequency of CTLps may have implications for organ graft survival and for donor selection in bone marrow transplantation--to do so on a routine basis.


Cytotoxic flow-cytometric crossmatches (flow-tox): a comparison with conventional cytotoxicity crossmatch techniques.

Detection and avoidance of donor-reactive antibodies in the sera of potential organ transplant recipients is key to a successful transplant outcome. Techniques of antibody detection that use flow cytometry are more sensitive than those that rely upon a visual determination of cytotoxicity. However, as conventionally performed, flow-cytometric crossmatches do not distinguish between cytotoxic (complement fixing) and noncytotoxic antibodies because both types of antibodies can bind to a cell and be detected by laser-activated fluorochrome photon emission. In 1989 we described two techniques for detecting cytotoxic antibodies using flow-cytometric techniques [1]. In 1990, we expanded the application of these new techniques that we called flow cytotoxicity assays or "Flow-Tox" [2]. Flow-Tox crossmatches demonstrate an increase in both sensitivity and specificity over conventional cytotoxicity crossmatches.


Diagnosis and management of the tethered cord syndrome.

Tethering of the spinal cord can occur from a thickened filum terminale, scarring due to myelomeningocele repair, lipomas or diastematomyelia. The typical presentation is a lumbar cutaneous defect, enuresis, unexplained back or leg pain, foot deformities, leg length discrepancies or scoliosis. Spinal ultrasound in neonates and MRI in older children offers ready diagnosis. With laser and microneurosurgical techniques, repair of these defects is safe and effective. The authors recommend that any infant having a mid-line lumbar cutaneous abnormality, such as a hemangioma, lipoma, hair patch or dimple, be evaluated to rule out tethering of the spinal cord.


The relationship between life expectancy and socioeconomic status in Arkansas: 1970 and 1990.

Life Expectancy at Birth is estimated for county populations in Arkansas in 1970, 1980 and 1990. Counties are grouped into quintiles at each time point according to the percent of persons below the poverty level. Comparisons are made between mean life expectancy in the highest and lowest socioeconomic group at each point in time as well as between the same group at 1970 and 1990. It is hypothesized that the high socioeconomic populations will experience an increase in mean life expectancy over the low socioeconomic populations between 1970 and 1990. Statistical analysis supports the hypothesis. These findings conform to those from earlier research in Ohio and may reflect a continuing deterioration in the relative standard of living of lower income groups in the United States subsequent to 1970.


A fully automated method for mononuclear bone marrow cell concentration.

We describe our experience in processing 40 bone marrow aspirates harvested for autotransplantation from patients with several hematological diseases using the CS-3000 blood cell separator. The bone marrow of the first 30 patients was processed by a semiautomated method, and a fully automated procedure was used for the remaining 10 cases. Both procedures were developed in our laboratory and yielded a similar average mononuclear cell recovery of 87.78% and 86.98%, respectively, and similar nucleated cell recovery (27.39% and 27.11%). The cloning efficiency of hematopoietic progenitor cells, measured as the total CFU-GM colony recovery in the in vitro cultures, did not differ between processed and recovered mononuclear cells. On the other hand, all the patients with transplants showed complete hematologic recovery, and the time to engraftment was similar to that described for other procedures. The automated procedure resulted in an average red cell removal of 97.81%, similar to the semiautomated procedure (94.19%), though with a narrower range (96.31-98.6% vs. 80.34-98.34%). The time taken to process a similar amount of bone marrow cell suspension was very different for each method: 1 hour for the fully automated vs. 2 1/2 hours for the semiautomated method to process 1,000 ml. Furthermore, the semiautomated procedure required the addition of homologous or irradiated plasma in a laminar air flow chamber, while the automated method is performed in a closed sterile system. We conclude that our procedure using the CS-3000 processor is an efficient method for fully automated large-scale processing of human bone marrow cells.


Analysis of venous access for therapeutic plasma exchange in patients with neurological disease.

We retrospectively analyzed our 2-year experience with venous access for 363 therapeutic plasma exchanges in 46 patients with neurological disease, including acute Guillain-Barré syndrome (N = 20), myasthenia gravis (N = 17), and chronic inflammatory demyelinating polyneuropathy (N = 9). Twenty-three patients (50%) completed the planned course of therapy using only peripheral venous access, and 28 central venous catheters were placed in the remaining 23 patients. Patients utilizing central venous access did not undergo a greater number of procedures, but they were more likely to have acute Guillain-Barré syndrome (P < 0.02) or to be hospitalized in a medical intensive care unit (P < 0.01). Three types of central catheters were used, and although our experience was predominantly with 1 type, differences were noted. Only 3% of procedures (3 of 96) done with a Quinton-Mahurkar catheter were associated with a catheter failure, compared to 27% (4 of 15, P < 0.01) with a Hickman catheter and 67% (2 of 3) with a triple-lumen catheter. Life-threatening complications occurred with 3 of 28 (11%) central catheters. To optimize the success of therapeutic plasma exchange using central access, it is critical that hemapheresis personnel advise each patient's primary physician regarding the type of central venous catheter required. Currently, we recommend use of a Quinton-Mahurkar or other dual-lumen hemodialysis catheter.


Artificial surfaces in apheresis devices: interactions with the complement system.

Blood contacts with artificial surfaces will effect different degrees of complement activation. Associated with complement activation will be cellular concentration and functional changes. The type of anticoagulant also will effect complement activation. The noted biomodulating effect of a material in contact with blood suggests that the choice and design of materials and their "biocompatibility" can be made to effect humoral and cellular changes as the therapy may require.


Basic principles of the ABO and Rh blood group systems for hemapheresis practitioners.

Since 1901, more than 20 distinct blood group systems have been identified and characterized. Yet, the ABO System, the first described, remains the most clinically significant in blood transfusion and organ transplantation medicine. The ABO antigens are the only cellular antigens which consistently produce a potent, naturally occurring antithetical antibody which circulates in the plasma of healthy individuals. ABO antigens are expressed on most blood cells, organs, and tissues and in most body fluids. Expression of the antigens results from the interaction of several separate, but closely related genes: ABO, H, and Secretor (Se). Blood group specificity depends upon the inheritance of the ABO and H genes, and the subsequent expression of these antigens on the red blood cells. The "D" or Rho antigen is the most clinically significant blood group antigen next to the ABO antigens. The D antigen belongs to the Rh System, which consists of a trio of genes that are so closely linked that they are inherited as a package. The antigens are an integral part of the red blood cell membrane. They lend stability to the membrane structure when they are normal, but result in decreased red cell survival when absent. Rh antibodies are immune antibodies requiring a stimulus and can cause significant transfusion and childbearing complications if present.


Basic principles of immunology (immune response) for hemapheresis practitioners.

Advances in medical knowledge and technology have identified the essential elements involved in the human immune system, their relationships and interactions, and offer more advanced concepts in the design, function, and maintenance of immune response. Immune response begins with the earliest progenitor cell and transfers its legacy of protection through white blood cells and the complement system. A basic understanding of immunology is essential to the hemapheresis practitioner as new treatment regimens requiring hemapheresis interventions develop.


Venous homografts in infra-inguinal procedures: an eight years experience.

Autogenous saphenous vein is still the first choice graft material for femoro-distal bypass whenever it is available, but the choice of an alternative is still a challenging problem. Between 1982 and 1989, 100 femoro-distal reconstructions were performed with saphenous vein segment homografts, harvested during varicose vein stripping, they were selected, prepared and stored at 4 degrees C. In 71 cases the distal anastomosis was below the knee. According to the actuarial life table analysis (Kaplan & Meyer) the cumulative graft patency rate after 6 months, 1, 3, 5 and 7 years was 79%, 63%, 46%, 45% and 42% respectively. Twelve cases of aneurysm formation or stenosis requiring reintervention occurred. The patency rate was not influenced by the site of the distal anastomosis, but the condition of the run-off vessels had a significant influence on the early occlusion rate. Varicose vein segments are a readily available source of graft material. The low cost, easy storage and handling of these grafts justify their use in limb salvage procedures.


Venous allografts for vascular reconstructions.

In order to evaluate various protocols for the preservation of venous allografts 162 arterial reconstructions were performed in mongrel dogs bypassing their ligated femoral arteries. The cumulative 6-month patency-rates as determined by weekly palpation and regular angiography were. Group I = Synthetic grafts: (a) Dacron 48%, (b) PTFE 53%. Group II = Fresh venous grafts: (a) autografts 100%, (b) allografts 37%. Group III = Veins preserved in saline at 4 degrees C for 1 month: (a) autografts 44%, (b) allografts 34%. Group IV = Veins preserved in saline at -70 degrees C: (a) autografts 58%, (b) allografts 47%. Group V = Veins preserved in glutaraldehyde solution: (a) autografts 26%, (b) allografts 22%. Group VI = Veins preserved in Hanks-solution with 15% DMSO at -160 degrees C: (a) autografts 77%, (b) allografts 35%. Histological as well as immunological studies suggest that these results are determined by the preservation protocol in Groups III, IV and V and by the presence of rejection in Groups I and VI. As the results with the allografts are not superior to those obtained with synthetic grafts, their use should be confined to those cases where the use of synthetic materials should be avoided at any price. Further experiments with immunosuppression and antigenic matching are indicated to see whether this would improve the results obtained with viable venous allografts.


An algorithm for the surgical management of chronic abdominal aortic occlusion and occluded aortofemoral grafts.

An algorithm for the surgical management of chronic abdominal aortic occlusion is presented based upon experience of treating 60 consecutive patients. Of 33 patients with juxtarenal aortic occlusion, 17 underwent aortofemoral bypass (AFB), 10 descending thoracic aortofemoral (DTAF), 5 axillofemoral (AxF) bypass, and 1 ascending thoracic aortofemoral bypass. Of 11 patients with mid or distal aortic occlusion, 8 underwent AFB, 2 DTAF and 1 AxF. Of 16 patients with aortic graft occlusion, 1 underwent AFB, 10 DTAF and 5 AxF. Acceptable risk patients were selected for AFB (26). DTAF (22) was frequently preferred for patients with occluded aortic grafts or other hazardous intraabdominal pathology. AxF (11) was used for patients with severe cardiopulmonary risk, limited life expectancy from malignancy, or when emergency procedures were required for salvage of severely ischemic limbs in debilitated patients with chronic aortic occlusion. In the AFB, DTAF and AxF groups the perioperative mortality was 8%, 5% and 36% respectively, the late mortality was 15%, 36% and 45%, and the 5-year primary cumulative graft patency was 92%, 89% and 15%.


Intralymphatic antibiotic delivery for reducing acute prosthetic graft infection.

The lymphatic system has been implicated as a source of synthetic graft contamination when grafts are implanted in the presence of a distal septic focus. In previous studies, radical lymphatic excision and ligation were shown to reduce acute graft sepsis. However significant lymphedema precluded its clinical application. The present study was undertaken to evaluate methods for reducing acute graft sepsis while avoiding lymphatic obstructive complications. Twenty dogs were divided into one control and two experimental cohorts. Femoral interposition grafts were placed in each dog. A hind paw septic focus was introduced and therapy included a control (Group I--no therapy), intravenous antibiotics in Group II and intralymphatic antibiotics in Group III. Graft, blood and tissue cultures from each dog were taken at 48 hours. Lymphatic antibiotic therapy resulted in significantly improved graft culture results when compared to the control (p = 0.0003) and intravenously treated animals (p = 0.007). Blood cultures in the intralymphatically treated group were also significantly better (p = 0.003) than the control group.


Aorto-femoral bypass and determinants of early success and late favourable outcome. Experience with 1000 consecutive cases.

Experience with 1000 cases of aorto-(bi)femoral bypass is presented evaluating factors influencing the overall patency rate and late survival, over a period of 25 years. There were 820 cases with bilateral and 180 with a unilateral bypass. Mortality was 3.3% and death rate 39.4%. Re-do procedures have been excluded. Operative indications were for stage I disease (moderate claudication) (17.6%), stage II (advanced claudication) (53.2%), stage III (rest pain and/or pregangrenous changes) (22.7%) and stage IV (gangrenous tissue loss (6.5%). Myocardial infarction was the predominant cause of late death in 192 cases (48.7%), followed by cancer in 48 (13%), cerebrovascular disease in 43 (11%), chronic lung disease with cor pulmonale in 15 (3.8%) and miscellaneous causes in 52 (13.2%) of patients. The cause of death was unknown in 31 (7.8%) cases. Co-existent peripheral arteriopathy (PAD) noted in 377 (37.7%) patients, was found to be a major determinant of late graft patency. Carotid artery disease and renovascular hypertension were corrected surgically, prior to aorto-femoral bypass in the 5.6% and concomitantly in 4.2%. Coronary artery disease in 273 (27.3%) patients and hypertension in 269 (26.9%), had a great influence on late survival as did age and smoking habits. Endarterectomy together with profundaplasty was carried out in 162 (16.2%) instances. It was our policy to extend the graft limb over the profunda femoris and in cases with co-existent superficial femoral artery disease 208 (20.8%). In 630 (63%) instances, the distal anastomosis was performed at the level of common femoral artery. Immediate graft patency was obtained in 99.3% of the cases. Late patency rate for stages I and II at 5, 10 and 15 years was 82%, 76% and 72% respectively. Following secondary operation for graft occlusion, the 15 year patency was increased to 71%. Co-existent superficial femoral disease can be alleviated by appropriate concomitant profundaplasty. Amputation rates were 0.8% for stage II, 1.5% for stage III and 2.4% for stage IV disease. Twenty year life table analysis showed a reduced survival (54%), in comparison with normal population (77%).


Management of solitary iliac aneurysms.

Eleven patients with isolated iliac artery aneurysms, presenting over a 10 year period, have been reviewed. Ten patients underwent surgery, of whom 3 had ruptured their aneurysms. Four patients had a solitary aneurysm, while the remaining 6 had 14 aneurysms between them. There was no operative mortality but 2 patients died of late vascular complications (after 4 and 12 months), 1 after proximal ligation only of an internal iliac artery aneurysm, and 1 after proximal and distal ligation and bypass of the common/external iliac artery for an aneurysm involving both the common and internal iliac arteries. Five patients had internal iliac artery aneurysms, and in 4 of these distal control was not achieved. Four patients died from unrelated disease (after 2-6 years). Safe control of internal iliac artery aneurysms cannot be achieved without distal internal iliac control.


Infected aortic aneurysms: CT diagnosis.

Infected aortic aneurysms are uncommon but important because they can lead to uncontrolled sepsis and/or aortic rupture. Symptoms are frequently minimal during the early stages and a high index of suspicion is essential to make the diagnosis. The surgical literature suggests that survival is markedly improved by a prompt diagnosis and aggressive surgical intervention. Our recent experience with 5 cases who underwent arteriography and/or computed tomography (CT) prior to surgery was reviewed and these diagnostic methods compared. Traditionally, arteriography has been considered indispensable in the evaluation of infected aortic aneurysms but the aneurysm lumen must reach a certain size before it can be detected and, even then, the extraluminal component may be underestimated. CT, with contrast enhancement, was more sensitive in the early stages of the disease and provided a more complete depiction of the anatomic abnormalities. Mural enhancement preceded the increase in the aortic lumen with disruption of aortic wall calcification. An earlier and more accurate diagnosis can be provided by CT than by angiography without the disadvantages of its invasiveness and cost.


Permeability changes following ischemia-reperfusion injury in the rabbit hindlimb.

Changes in permeability following ischemia-reperfusion injury were assessed in the intact rabbit hindlimb by measuring the transvascular clearance of 125I-labeled rabbit serum albumin. Ischemia was induced for periods of 1 or 2 hours by use of a pneumatic tourniquet inflated to 300 mmHg. Following ischemia, the limb was reperfused for 1, 2, or 3 hours. The albumin clearance in the gastrocnemius muscle of control rabbits was 5.1 +/- 0.7 (mean +/- SEM) microliters/hr/g dry weight. Following 1 hour of ischemia and reperfusion, muscle albumin clearance rose to 71.4 +/- 26 microliters/hr/g dry weight which was not significantly different from those animals that underwent 2 hours of ischemia. Muscle albumin clearance continued to be elevated following 2 hours of reperfusion; however, it returned toward control levels after 3 hours of reperfusion. These data suggest there is a transient increase in albumin permeability following ischemia-reperfusion injury in skeletal muscle.


An experimental study to examine the patency and tissue response of two types of biosynthetic graft used as a replacement for porcine inferior vena cava.

This experimental study has been carried out to evaluate biosynthetic grafts as vascular substitutes. Tubular segments of 35 x 8 mm made of (1) tanned ovine collagen and integral polyester mesh, either of the first (Omniflow I) or second generation (Omniflow II), or (2) polytetrafluoroethylene (e-PTFE), have been sutured in the infrarenal inferior vena cava of pigs, and removed 1 hour, 7, 14, 28, 56 and 112 days after implantation. The patency rate of biosynthetic grafts was higher than that of e-PTFE grafts (p < 0.01). There was no significant difference between the patency of the first generation and second generation collagen grafts. These results indicate that biosynthetic prostheses may be suitable vascular substitutes in low flow and low pressure systems. Improvements in the collagen inner cover structure (Omniflow II vs. Omniflow I), producing greater mechanical endurance, did not enhance long-term patency or the healing patterns of biosynthetic grafts.


Pre- vs postoperative pharmacologic inhibition of platelets: effect on intimal hyperplasia in canine autogenous vein grafts.

Several clinical studies have shown that pharmacologic inhibition of platelets can increase the patency of vascular grafts, but only if platelet-inhibition is initiated before surgery. This study was performed to compare the efficacy of pre- vs postoperative platelet-inhibition on the development of intimal hyperplasia in canine autogenous vein grafts. Reversed femoral veins were used to bypass the ligated femoral arteries in 15 dogs. End-to-side anastomoses were constructed. Eleven dogs were treated with aspirin (325 mg QD) and dipyridamole (25 mg BID). In six dogs treatment was begun 48 hours preoperatively and continued for 3 months. In five other dogs treatment was begun 48 hours after surgery and was continued for 3 months. In 4 control dogs no antiplatelet treatment was given. Excision of the vein grafts 3 months after surgery disclosed reduced intimal hyperplasia (p < 0.05) in the grafts excised from all of the treated animals as compared with those obtained from the control animals. However, there was no difference in intimal hyperplasia observed in the dogs treated both pre- and postoperatively (11 grafts) as compared with those treated only postoperatively (9 grafts). These data demonstrate that it is not necessary to begin antiplatelet therapy preoperatively in order to inhibit intimal hyperplasia. They also suggest that preoperative antiplatelet therapy may improve early graft patency by directly preventing thrombosis, not by inhibiting the development of intimal hyperplasia.


Importance of valvular incompetence after acute deep venous thrombosis.

The color Doppler scanner was used to analyze acute deep venous thrombosis in 14 patients. A thrombus was found in the superficial femoral vein in 4 patients and in the superficial femoral and popliteal veins in 6 patients; a popliteal occlusion was found in 4 patients. All 14 patients were treated with intravenous heparin followed by at least 3 months of warfarin therapy. Patients were re-examined between 24 and 48 months. Six patients were symptomatic; 8 were asymptomatic. Five patients had occluding thrombus in the distal popliteal vein; major competent collateral channels developed from the proximal superficial femoral vein, and they remained asymptomatic. Three patients whose superficial femoral veins recanalized without valvular incompetence were asymptomatic. Valvular incompetence was observed in all of the symptomatic patients. Patients with persistent popliteal occlusion and collateral channels have fewer symptoms than patients with valvular incompetence in the superficial femoral and popliteal veins.


Comparison of heated-probe laser Doppler and transcutaneous oxygen measurements for predicting outcome of ischemic wounds.

Transcutaneous oxygen (TcPO2) measurement has proven to be an accurate means of predicting healing of ischemic wounds. This study compares the ability of TcPO2 and laser Doppler, modified by the addition of a heated probe (LDHP), to assess wound outcome. TcPO2 and LDHP measurements were made at the same site for 80 wounds, which consisted of 51 amputations (25 above knee, 6 below knee, 20 forefoot) and 29 ulcerations. Healing was defined as complete wound closure. Failure to heal was defined by the necessity for proximal amputation in 22 wounds (6 amputations, 16 ulcers). Outcome criteria were chosen to maximize accuracy and either positive or negative predictive values. Criteria with the greatest accuracy and positive predictive value for wound healing were > or = 11 mmHg for TcPO2 and > or = 50 mv for LDHP range. Criteria with the most appropriate accuracy and negative predictive value for wound failure were < 5 mmHg for TcPO2 and < 35 mv LDHP range. All wounds whose LDHP range was < 35 mv failed to heal, whereas some wounds with a TcPO2 of 0-1 mmHg healed successfully. An absolute prediction of wound healing (100% specificity and negative predictive value) was offered when either LDHP range was > or = 125 mv or TcPO2 was > or = 33 mmHg, although accuracy of either measurement at this criteria was unacceptable for more general application. We conclude that TcPO2 or LDHP will assess wound outcome with similar overall accuracy, although each test may be better for predicting a specific outcome.


Long-term results of the surgical management of symptomatic chronic intestinal ischemia.

We analyzed our surgical experience in 20 patients who underwent revascularization procedures for symptomatic chronic intestinal ischemia caused by atherosclerosis. The group comprised 17 women and 3 men, with an age range of 25 to 71 years (mean 58.6 years). Sixteen patients had postprandial abdominal pain, and 4 had pain not related to eating. The average weight loss was 23.8 lb. Malabsorption and diarrhea were present in 8 patients. The duration of the symptoms was from 4 to 46 months (mean 13.4 months). One patient presented with acute intestinal ischemia following balloon angioplasty reocclusion of a stenotic celiac artery, and 3 underwent surgery for stenosis of a previously placed graft. Five patients had single mesenteric artery involvement, 10 had double-artery involvement, and 5 had significant occlusion in all 3 mesenteric arteries. The major arteries were revascularized whenever technically possible; therefore, 36 arteries were revascularized in 20 patients. Bypass grafts were done in 27 vessels, reimplantation in 7, and endarterectomy with patch angioplasty in 2. The saphenous vein was used in 12 vessels, polytetrafluoroethylene grafts in 8, dacron in 6, and inferior mesenteric vein in 1. The type of revascularization or graft utilized did not affect long-term patency. Two patients had early graft thrombosis and required intestinal resection. All patients survived the operation. At a mean follow-up of 36 months, all 20 patients were alive and asymptomatic with regard to their abdominal complaint. Ten patients (50%) underwent postoperative abdominal angiography; all the grafts were patent.(ABSTRACT TRUNCATED AT 250 WORDS)


Profunda femoral artery pseudoaneurysm after percutaneous transluminal procedures manifested by neuropathy.

The incidence of arterial complications following femoral artery cannulation is low; however, with the increasing number of cardiac diagnostic and interventional procedures, vascular surgeons are being confronted with an increasing number of pseudoaneurysms and arteriovenous fistulas. Swelling and a painful pulsating groin masse are the most frequent presenting symptoms of a common femoral artery false aneurysm. We present the cases of 4 patients who had the unusual finding of a profunda femoral artery pseudoaneurysm after they had undergone cardiac catheterization or percutaneous transluminal coronary angioplasty. The only clinical sign of these patients was femoral neuropathy or neuropalsy caused by femoral nerve compression. Surgical repair of the pseudoaneurysm was successful in all patients. We discuss the reasons for this unusual finding and rare location for a pseudoaneurysm.


Salmonella infection of a Dacron aortic bifurcation graft.

We report a case of primary salmonella infection of a dacron aortofemoral bypass graft. Local graft excision with extra-anatomic bypass resulted in a successful outcome. Salmonella, whilst the commonest cause of infected abdominal aortic aneurysms, is currently a rare cause of prosthetic graft infection. However, given the increasing prevalence of salmonellosis in the community, we believe this situation will change and surgeons should be alert to this new and dangerous addition to the list of graft pathogens.


Pretreatment with H2 blocker famotidine to ameliorate protamine-induced hypotension in open-heart surgery.

An antagonist to H1 histamine receptor and one to H2 histamine receptor were used to prevent protamine-induced hypotension in 126 Japanese patients undergoing open heart surgery. In a study comparing an H1 antagonist "diphenhydramine" and an H2 antagonist "famotidine", 103 patients were divided into four groups: 31 patients were given no drugs (Group 1), 25 patients were given 0.4 mg/kg of diphenhydramine (Group 2), 33 patients were given 0.4 mg/kg of famotidine (Group 3), and 14 patients were given both the drugs (Group 4) before protamine administration. Although the systolic arterial pressure decreased significantly after protamine administration in all groups, famotidine was found to be effective in reducing protamine-induced hypotension, whereas diphenhydramine was not effective. In order to further investigate the hemodynamic changes in a double-blinded fashion, 12 patients were given normal saline (Group 5), while 11 patients were given 0.4 mg/kg of famotidine (Group 6) before protamine administration. Again, the minimal systolic and mean arterial pressures after protamine injection were significantly higher in Group 6 than in Group 5, while left atrial pressure, central venous pressure, heart rate, and cardiac index were almost the same and remained constant in the two groups. These results strongly suggest that the H2 antagonist "famotidine" is beneficial in reducing protamine-induced hypotension after cardiopulmonary bypass, while the H1 antagonist "diphenhydramine" is not.