Etretinate or cyclosporin-A treatment normalizes the enhanced respiratory burst of polymorphonuclear leukocytes in psoriasis. During a therapeutic trial to treat psoriasis with either etretinate or cyclosporin A (CyA) we measured the respiratory burst activity of polymorphonuclear leukocytes (PMN). Six patients received 0.5-0.75 mg/kg etretinate and 14 patients 2.5-5.0 mg/kg CyA over a period of 10 weeks. The extent of psoriasis was graded by the psoriasis area-and-severity index (PASI score). The respiratory burst of PMN isolated from the peripheral blood was measured employing luminol-enhanced chemiluminescence at weeks 0, 3 and 10 and compared with that of 26 healthy control individuals. PMN were stimulated with zymosan particles, aggregated immunoglobulin (aggIg) and concanavalin A (ConA). Both treatment regimens improved psoriasis; at 10 weeks there was an approximate 40% PASI score reduction under etretinate and an 80% improvement under CyA. Before treatment the respiratory burst was abnormally high under stimulation with the three stimuli in patients (p = 0.021 to less than 0.0001). After 3 to 10 weeks PMN activity normalized in all patients and even tended to drop below values correlating with an improvement in skin lesions. We conclude that the elevated respiratory burst of PMN in psoriasis normalizes under treatment with both etretinate and CyA.


Induction and repair of UVB-induced cyclobutane pyrimidine dimers and (6-4) photoproducts in organ-cultured normal human skin. To examine the induction and repair of UV-induced DNA damage, indirect immunofluorescence was performed on UVB-irradiated organ-cultured normal human skin using monoclonal antibodies specific for either cyclobutane pyrimidine dimers or (6-4) photoproducts. Nuclear immunofluorescence of cyclobutane pyrimidine dimers and (6-4) photoproducts were observed in a dose-dependent manner after UVB irradiation. The intensity of nuclear immunofluorescence of the upper epidermal layers was stronger and clearer than that of the lower epidermal layers. DNA repair time-course studies showed that both types of DNA damage could be repaired within 24 h after UVB irradiation.


Measurement of S phase duration in human epidermis using cyclin immunostaining and 3H-thymidine pulse labelling. Cyclin/PCNA (proliferating cell nuclear antigen) is a nuclear protein strongly associated with DNA replication sites. Under methanol fixation, cyclin immunostaining might serve as a specific marker for S-phase cells. Associated with single labelling with 3H-thymidine, this immunodetection represents an easy method for measuring S-phase duration. Its application to six samples of normal human epidermis allowed us to measure an S phase of 9.7 +/- 0.3 h, a result in fair agreement with a previous estimate of 10.2 h obtained from a classical double-labelling technique with two different concentrations of 3H-thymidine.


Ultrastructural localization of actin in normal human skin. Normal human skin was embedded in Lowicryl K4M. Actin microfilaments were localized by applying a postembedding immunogold technique using the monoclonal anti-actin antibody HHF35. Actin microfilaments are part of the cytoskeleton in muscle and nonmuscle cells. Together with myosin they produce contraction. The antibody labelled myofilaments in smooth muscle arrector pili cells, myoepithelial cells and pericytes. In sweat gland cells the microvilli system, a zone beneath the cytoplasma membrane corresponding to the adhesion belt region, and apocrine decapitation formations showed labelling.


Identification of a cell layer containing alpha-smooth muscle actin in the connective tissue sheath of human anagen hair. Immunohistochemical and immunoelectron microscopy studies revealed the presence of alpha-smooth muscle (alpha-SM) actin in fibroblasts located in the connective tissue sheath (CTS) of human anagen hair follicles. Immunostaining was positive from the base of the bulb to the upper part of the lower portion of the mature anagen hair follicles. The late catagen hair follicles did not stain. Ultrastructurally, alpha-SM actin was detected only in the fibroblasts located in the innermost layer of the transverse collagenous fibres. Since alpha-SM actin is located in cells with contractile potential, this newly identified layer may play an important role in the morphological changes of the lower portion of the hair follicle during the hair growth cycle.


A practicum in private practice for graduate students in psychiatric nursing. Clinical placements in psychotherapy for graduate students in psychiatric nursing are getting difficult to find because of bureaucracy, liability issues, competition, and safety and convenience concerns in urban areas. One solution is to design a placement in private practice.


Borderline omnipotence in pathological gambling. Borderline omnipotence in pathological gambling is examined, including psychodynamics of omnipotence, a theory of the client's use of omnipotence in pathological gambling, and the effects of omnipotence on the treatment and recovery of the pathological gambler. Assessment, staff education, and the need for individualized treatment for the pathological gambler are discussed.


Gender issues and borderline personality disorder: why do females dominate the diagnosis? There are significantly more females with the diagnosis of borderline personality disorder than males. This article explores the developmental factors that place females at a greater risk to develop the disorder. Societal expectations that increase the emerging of borderline symptoms are also discussed. Gender differences of "normal" behavior that effect the assigning of the diagnosis are explained. The theory that borderline personality disorder has become the "virus" of psychiatry is presented.


Masochism: implications for psychiatric nursing. Psychiatric nurses often encounter patients who seem to be victims of negative circumstances and are unable to reverse these situations. This article explores the phenomenon of masochism as an outcome of the fear of separation or abandonment. A unified theory is presented, and a case is used to demonstrate the theory.


Pathological infatuation or the Blue Angel syndrome. The term masochism has undergone an evaluation since first being introduced solely in relation to sexual perversion by Kraft Ebing in 1906. Masochism can be defined as any behavior that is repetitively self destructive. Relationships in which partners sacrifice themselves and their own best interests can be considered masochistic. There is a difference between a normal pattern of falling in love and a masochistic pattern. The concept of pathological infatuation or what this author has termed the Blue Angel syndrome is presented. A case history with clinical examples is examined to further illustrate these concepts.


Subspecialization within psychiatric consultation-liaison nursing. Specialization within health care is evolving in response to the proliferation of knowledge about disease treatment and health management. The practice of psychiatric consultation-liaison nursing in the acute care hospital is diversifying through subspecialization as a result of this trend. This article examines the concept of subspecialization within psychiatric consultation-liaison nursing practice. Subspecialization is presented as a safeguard for professional viability and as a hallmark of quality consumer care. Specialization has advantages and potential disadvantages for nursing practice. Strategies are described that maximize the benefits and minimize the disadvantages of subspecialization.


Psychic loss in adult survivors of father-daughter incest. Studies show that adult survivors of childhood incest comprise a significant percentage of female psychiatric patients. The varied and multidetermined presenting symptomatology of these patients frequently leads to misdiagnosis and treatment interventions that fail to address core issues of the incest experience. One such issue is the child's experience of the psychic loss of a physically present parent that is part of the emotional trauma of incest. The goal of this paper is to discuss psychic loss as a core element of the incest experience, particularly in father-daughter incest, and to describe the conditions of childhood mourning that inhibit successful resolution of this loss. Attention is addressed to the psychoanalytic understanding of mourning as a basis for interventions in the treatment of adult survivors.


Female sexual abuse survivors as patients: avoiding retraumatization. The literature on adult female psychiatric patients who are survivors of childhood sexual abuse is reviewed. This literature shows both high rates of such abuse and a characteristic pattern of symptoms that distinguishes these survivors from other patients. A theoretical framework is discussed which explains how psychiatric symptoms may develop after childhood sexual abuse and how diagnosis and treatment may serve to maintain or intensify such symptoms. Viewing patients from a posttraumatic treatment perspective is advocated as a strategy for nursing to effectively help these patients with the healing process.


Clinical significance of mucin production in post-irradiated cervical carcinoma. Histological sections from 50 patients with clinical stage Ib to stage IIb squamous cell carcinoma of the cervix, initially treated by radiotherapy and followed by Wertheim hysterectomy, were reviewed and stained for mucin. The tissues from 17 (34%) of the patients contained no residual carcinoma. Mucin production was demonstrated in tumour tissue from 18 (55%) of the patients with residual tumour, none of who died of disease during the 5 to 10 years of follow up. Two patients who died of recurrent carcinoma had no mucin production in the post-irradiated tumour tissues. The presence of mucin in irradiated carcinoma of cervix seems to infer a better prognosis and this may prove useful in the follow-up of irradiated carcinomas.


Pregnancy with an intrauterine device in situ and preterm delivery. We determined the prevalence of preterm delivery in a population of women who conceived with an IUD in situ and compared the results with those in a group of women without any contraceptive method. The study group consisted of 16 women who conceived with a copper IUD in situ. The control group comprised 48 women matched for age, gravidity and parity. The prevalence of preterm delivery was significantly higher in the study group than in the control group (18.7% (3/16) vs 2% (1/48)), respectively. (P = 0.045, Fisher's exact test.)


Condition at birth of infants with previously absent or reverse umbilical artery end-diastolic flow velocities. In a case control study we assessed 47 fetuses with absent or reverse end-diastolic flow velocities (AREDFV) of the umbilical artery with respect to the mode of delivery, fetal acidosis, and abnormal neurological evaluations at the time of discharge from the department of pediatrics. We also studied a control group which was matched for gestational age and had normal umbilical artery flow velocity waveforms. Fetuses with AREDFV were delivered almost exclusively by cesarean section which was usually done for fetal distress. The number of fetuses with abnormal neurological signs was significantly increased compared to the control group. Fetuses with AREDFV showed an increased incidence of fetal acidosis. Forty per cent of these fetuses were delivered within one day of the first abnormal flow measurement; Sixty per cent were observed clinically for up to four weeks before delivery.


Reproductive performance after local and systemic prostaglandin for ectopic pregnancy. The injection of different substances into early, unruptured tubal pregnancies is increasingly advocated. In this study, fertility was evaluated after treatment of tubal pregnancy by means of prostaglandins. The overall tubal patency rate was 86.4% and 14 of 20 patients (70%) could subsequently achieve pregnancy.


Influence on erythropoietin levels of treatment with cisplatinum-endoxan. Erythropoietin levels have been determined in 24 patients with different gynecologic malignancies, who were treated with cisplatinum and endoxan. A statistically highly significant decrease was demonstrated 2 h after starting treatment with a further significant decrease at 6 h. After 12 h the erythropoietin concentrations returned to values similar to those before treatment started.


Culdocentesis is an obsolete diagnostic tool in suspected ectopic pregnancy. We studied 332 patients with proven pregnancies. Prediction of hemoperitoneum by assessment of the Douglas pouch during bimanual examination had a false negative rate of 42.1%. The false negative rate for culdocentesis was 14.8%. It is therefore concluded that culdocentesis is not a useful tool in the diagnosis of suspected ectopic pregnancies.


Congenital chylothorax in a trisomy 21 newborn. We here report a case of trisomy 21 with congenital chylothorax. The patient was a male newborn who had been diagnosed as having trisomy 21 with congenital chylothorax. This is the fifth case of the both conditions in English literature. Congenital chylothorax is very rare in a trisomy 21 patient. There, however, may be causal relationship between the two conditions.


[Substitution of inferior vena cava for Gore-Tex ring prosthesis: experimental study]. We conducted an experiment in 10 mini-pigs, using the Goretex prosthesis to replace the inferior vena cava. Venous flow was increased by a distal arterio-venous fistula to reduce the risk of thrombosis. The survival rate at 3 months was 60%. The foregoing results indicate that this replacement procedure should be considered in inferior vena caval replacement which, although rarely, might be warranted in the clinical course of renal adenocarcinoma.


[Surgical adrenal gland pathology. Urologist's pathology]. We reviewed 6 cases of unilateral adrenal tumor that had been treated during a 5-year period. The Turner-Warwick modified lateral approach was performed in all 6 cases. In our view, surgical treatment of unilateral adrenal tumors should be performed by the urologist. The high lumbar approach appears to be the most appropriate for unilateral adrenal tumor masses not larger than 6 cm. The surgical anatomy of the adrenal gland is briefly described.


[Calcifications in renal adenocarcinoma. Image assessment in 17 cases]. Of 60 renal adenocarcinoma tumors that had been diagnosed at our hospital between 1984 and 1990, 17 had presented intratumoral calcification. These 17 tumors with calcification were studied to assess the sensitivity of different techniques relative to detection, localization and morphologic characterization of the calcifications. We can conclude from the study that the use of CT and US not only raised detection rate (28%), but also permitted more precise evaluation of the calcified tumor mass. Furthermore, tumor spread beyond the calcified area was found to be a sign of malignancy.


[Usefulness of catheter pyelography in ileal diversions and continent bladder replacement after radical cystectomy]. Transcatheter ascending pyelography is commonly performed in the post-operative evaluation of patients submitted to ileal diversion or continent bladder replacement after radical cystectomy. The present study investigated the usefulness of this procedure in the control of these patients. Of 51 patients that underwent cutaneous ileal diversion, the IVP revealed a leak of the contrast medium in only one case (1.9%). Of the 18 patients that received a continent neobladder, radiologic signs of changes were detected in 6 cases (33.3%). The complications of the IVP in our patients were fever in 26 patients (37.7%) and septicemia in one patient (1.45%). Considering the information obtained and the rate of morbility, we believe that ascending pyelography through catheters is not justified in the routine post-operative control of patients who have undergone radical cystectomy and ileal diversion. However, it appears to be a useful procedure in those cases that have undergone bladder replacement and/or continent diversion procedures.


[Behavior of the contralateral ureter following surgery for unilateral antireflux surgery]. We present our experience of 44 cases with unilateral vesicorenal reflux that had been treated by ureteroneocystostomy using the Cohen technique. The reflux disappeared in 32 cases, it appeared in the contralateral ureter in 7 patients, it was ipsilateral in 2 and bilateral in 3. Of the 10 cases with contralateral reflux, 2 required surgery, while 8 were amenable to medical treatment. In our series, contralateral reflux appeared at random. Since the spontaneous cure rate was 80%, we believe that bilateral antireflux surgery for unilateral reflux is unwarranted. Urodynamic studies can be important in the indication for conservative treatment.


[High flow priapism].

[High flow priapism]. Four cases with high flow priapism are described herein. Patient evaluation included intracavernal blood-gasmetry, echo Doppler, selective arteriography of the pudendal artery. Three patients had a previous history of trauma and one patient was on psychotropics. The alpha-agonist drugs and the different shunt techniques did not achieve detumescence. Two embolization procedures of the internal pudendal artery were performed with good long-term results. The other two cases achieved spontaneous detumescence. No complications or secondary erectile dysfunction were observed.


[Integral urologic echography: retrograde sonourethrography]. Herein we describe a new technique for urethral exploration which replaces conventional radiological urethrography to a large extent. Retrograde sonourethrography is capable of providing data different from those of radiology, eliminates most of the inconveniences of the radiologic techniques and provides images of the entire trajectory of the urethra. Because this procedure can be repeated as often as necessary, it is the diagnostic procedure of choice in urethral stricture, a persistent and recurrent pathological condition. The results of a study conducted in 30 patients with different urethral pathologies are presented.


[Endoscopic resection of tumor of the renal pelvis]. We report on a patient who was submitted to percutaneous resection of a solitary, low grade urothelial transitional cell tumor of the renal pelvis. A review of the literature shoned endourologic treatment to be a valid in carefully selected cases. The measures to minimize the risk of tumor spread and the good results obtained are discussed. However, a longer follow up and larger series are necessary in order to draw definitive conclusions.


[Spontaneous extravasation of urine secondary to bladder carcinoma. Non-invasive therapy]. A case of spontaneous urinary extravasation secondary to bladder carcinoma is described. The patient received systemic polychemotherapy which reduced tumor size and resolved renal ectasia and urinary extravasation. Spontaneous urinary extravasation secondary to bladder carcinoma is rare. For this reason we considered it of interest to report this case.


[Fistula between ileal conduit and small intestine after cutaneous ureteroileostomy]. We report on a case of ileal conduit-enteric fistula which appeared early after ureteroileostomy using the Bricker technique. The appearance of gastrointestinal content through the stoma was the only sign. An ileogram permitted making the diagnosis. Conservative treatment was instituted and the fistula resolved spontaneously. The different diagnostic and therapeutic aspects of this uncommon complication after ureteroileostomy are discussed.


[Urachal leiomyoma].

[Urachal leiomyoma]. A case of leiomyoma of the urachus is reported herein. A review of the literature revealed only 6 cases have been reported. Its incidence is suspected to be higher, but this tumor type is only detected when it is large enough or when complications arise such as bleeding, infection, etc. There is no other data of interest except for its rarity.


[Renal transplant and cutaneous ureteroileostomy. Report of 2 cases]. Congenital or acquired pathology of the lower urinary tract currently does not preclude renal transplantation in patients with end-stage nephropathy. We report two cases of renal transplantation with ureteroileal cutaneous diversion in patients with a nonfunctional lower urinary tract due to bladder fibrosis secondary to urinary tuberculosis. We discuss the possibilities of the urodynamic study in the preoperative evaluation of patients with similar conditions.


[Multiple organ metastasis following nephrectomy for renal carcinoma]. We report a case of TNM stage II renal carcinoma with metastasis to lungs, contralateral adrenal gland and skin within 5 years following nephrectomy. The patient underwent lobectomy, adrenalectomy and cutaneous excision biopsy. The clinical course and management of metastases are discussed.


Recovery from pulmonary hypertension in an adolescent with mixed connective tissue disease. This paper describes the case of an 11 year old girl who presented with mixed connective tissue disease which was complicated by the development of pulmonary hypertension. This case is unique with respect to the young age of onset, the serial non-invasive method used to follow the disease process, and the favourable response to treatment with vasodilator and anti-inflammatory drugs.


Palmar rheumatoid nodulosis associated with local pressure. Rheumatoid nodulosis is a term used to describe adult patients with rheumatoid arthritis with little or no clinical joint inflammation who have numerous subcutaneous nodules indistinguishable from those of patients with active rheumatoid arthritis. This paper reports the case of a woman with quiescent rheumatoid arthritis who developed palmar nodulosis three weeks after the strenuous activity of painting her apartment. This case illustrates the direct association between the appearance of nodulosis and physical pressure despite inactive disease.


Long term treatment of chronic Lyme arthritis with benzathine penicillin. The cases are reported of two patients with chronic Lyme arthritis resistant to the recommended antibiotic regimens who were cured by long term treatment with benzathine penicillin. It is suggested that the sustained therapeutic levels of penicillin were effective either by the inhibition of germ replication or by lysis of the spirochaetes when they were leaving their sanctuaries.


Ulcerative colitis complicating seronegative HLA-A2-B27 rheumatoid arthritis with sacroiliitis. The case is reported of a 50 year old man with longstanding seronegative rheumatoid arthritis who developed ulcerative colitis. The patient also had sacroiliitis and his tissue was typed as HLA-A2-B27 several years before the bowel disease began. A possible overlap between primary inflammatory bowel disease, complications to the treatment of rheumatoid arthritis with drugs, and gastrointestinal rheumatoid vasculitis is discussed.


A 12 year follow up study in the general population on prognostic factors of cartilage loss in osteoarthritis of the knee. The natural history and prognostic factors of cartilage loss in osteoarthritis of the knee were studied in subjects from a general population survey on rheumatic diseases in 1975-8. Baseline data were collected by questionnaire, physical examination, and weightbearing anteroposterior knee radiographs. Follow up of the subjects aged 46-68 years with radiological osteoarthritis grade 2-4 (Kellgren) took place in 1988-9. Cartilage loss was assessed by two observers who scored the change in joint space width between two radiographs. Thirty four per cent had cartilage loss. Prognostic factors and adjusted odds ratios (ORs) (95% confidence intervals) were: body mass index OR = 11.1 (3.3 to 37.3) fourth v first quartile; body weight OR = 7.9 (2.6 to 24.0) third v first tertile; age OR = 3.8 (1.1 to 13.4) > 60 v < or = 49 years; Heberden's nodes OR = 6.0 (1.5 to 23.1); clinical diagnosis of generalised osteoarthritis OR = 3.3 (1.3 to 8.3); and previous bow legs or knock knees OR = 5.1 (1.1 to 23.1). The relation of age with cartilage loss was also confounded by the presence of Heberden's nodes or a diagnosis of generalised osteoarthritis. There was no statistically significant relation for gender, meniscectomy, injury, uric acid concentration, chondrocalcinosis, smoking, and occupation related factors, except possibly standing.


Scintigraphic assessment of osteoarthritis of the knee joint. Clinical, radiographic, and scintigraphic abnormalities of the knee joint have been correlated in a cross sectional study of 100 patients with osteoarthritis. The group comprised 73 women and 27 men with a mean age of 65.7 years. One hundred and ninety one of the 200 knees had clinical (175) or radiographic (185) evidence of osteoarthritis, or both (161). Scintigraphic images of the knees were obtained 4-5 minutes (early phase) and 2.5-3.5 hours (late phase) after intravenous injection of 600 mBq of technetium-99m diphosphonate. Abnormal images were recorded in 162 knees (81%), and six different patterns were detected. Generalised isotope retention around the knee (early or late phase) was less common than focal areas of uptake around the joint margin (early or late phase) or in the patella or subchondral bone (late phase). Some knees with abnormal scans were normal on radiography (n = 7), or vice versa (n = 21). Different scan patterns correlated with different clinical and radiographic features: the generalised pattern correlated with pain (odds ratio (OR) = 45.1) and osteophytes (OR = 48.3); joint line retention correlated with subchondral bone sclerosis on radiography (OR = 62.1); and subchondral bone retention correlated with more severe radiographic changes. It is concluded that different patterns of scintigraphic abnormality reflect various aspects of the disease process of osteoarthritis.


Effect of disease severity on rheumatoid arthritis concordance in same sexed siblings. To assess the factors in a proband with rheumatoid arthritis (RA) that might predict the occurrence of the disease in siblings, 240 same sexed sibships (190 female, 50 male) in which the proband had classical or definite RA were clinically and immunologically documented. Sibship concordance rates were consistently higher for features of severe disease in the proband, reaching statistical significance for a clinical score of disease severity (the SS index). This trend for increasing disease severity to be associated with increasing sibship concordance rates could not be accounted for by age or disease duration of the proband. These results suggest that siblings of probands with severe RA are at greater risk of developing RA than those of probands with mild disease.


Ankylosing spondylitis and monoclonal gammopathies. From 1960 to 1990, 557 patients with ankylosing spondylitis (428 men, 129 women) were diagnosed and indexed in the department of rheumatology. Monoclonal gammopathies were found in seven (five men, two women) patients (1.3%). With one exception, ankylosing spondylitis preceded monoclonal gammopathies by many years. The distribution of the isotypes of the mIg found in these seven patients was striking when compared either with previous reports of an association between ankylosing spondylitis and monoclonal gammopathies or with local data on the epidemiology of monoclonal gammopathies: five patients with IgG, four of them of the lambda (lambda) type, and two IgM, both of the kappa (kappa) type were found; no patients with mIgA were recorded. Two patients were HLA-B27 positive and had slight and transient monoclonal gammopathies, whereas three subjects were HLA-B27 negative and had important spikes, corresponding in two subjects to malignant diseases. This observation raises the question of whether the coexistence of HLA-B27 and ankylosing spondylitis might provide a protective action. Epidemiological studies are required to clarify such points.


Cellular immunity to cartilage proteoglycans: relevance to the pathogenesis of ankylosing spondylitis. Cellular immunity to cartilage proteoglycans may be responsible for sustaining chronic inflammation in ankylosing spondylitis. This hypothesis was examined by measuring peripheral blood and synovial fluid mononuclear cell proliferation in five preparations of human cartilage proteoglycan monomer in vitro. Peripheral blood mononuclear cells from 25 patients and synovial fluid mononuclear cells from five patients were compared with those from normal and disease control subjects matched for age. No significant differences were found between the three groups. This suggests that autoimmune responses to cartilage proteoglycans are unlikely to play a significant part in the pathogenesis of ankylosing spondylitis.


Plasminogen activators in synovial fluid and plasma from patients with arthritis. The activity of plasminogen activators and inhibitors in the synovial fluid and plasma of patients with various forms of chronic arthritis was characterised. Tissue-type plasminogen activator antigen (t-PA:Ag), urokinase-type plasminogen activator antigen (u-PA:Ag), the proenzyme single chain u-PA (scu-PA), and plasminogen activator inhibitor (PAI) were measured in the synovial fluid and plasma of 22 patients with seropositive rheumatoid arthritis (RA), 13 with seronegative RA, and 23 patients with various forms of arthritis. In all patient groups the levels of t-PA:Ag in synovial fluid were lower and the levels of u-PA:Ag and PAI higher than plasma levels. Synovial fluid u-PA was more activated than plasma u-PA. Comparison of the patient groups showed that the largest differences between fibrinolytic parameters in synovial fluid and plasma were present in patients with seropositive RA followed by patients with seronegative RA and patients with various forms of arthritis. This order paralleled the functional and radiological scores of joint destruction in the patient groups studied. The results of this study indicate that suppression of t-PA production and enhancement of u-PA synthesis and activation in arthritic joints are associated with the clinical severity of arthritis.


Action of sodium aurothiomalate on erythrocyte membrane. The number of sulphydryl groups on the erythrocyte membrane has been assessed as a function of nutritional status for two groups of patients, one receiving non-steroidal anti-inflammatory drugs (NSAIDs) and the other receiving sodium aurothiomalate (Myocrisin). The patients receiving NSAIDs had a significantly higher number of sulphydryl groups in both the glucose depleted and glucose activated states than the patients receiving sodium aurothiomalate. The study focuses on the hexose transport protein where there is a specific binding site for gold using the two sulphydryl residues on helices 11 and 12 of the protein. The data suggest that the strong binding of gold to the erythrocyte membrane occurs via thiol pairs rather than by isolated sulphydryl groups and that there are possibly two further binding sites for gold on the membrane, the identities of which are still unclear.


Night pain in arthritis: patients at risk from prescribed night sedation. To assess the problem of night pain and the use of hypnotic drugs in patients with rheumatic diseases 165 consecutive patients (mean age 58.5 years) were assessed and questioned about night pain and the use of drugs including night sedation. Most of the patients (106 (64%)) were women. A total of 32 (19%) patients were receiving night sedation for a mean duration of 43.9 months. Fourteen patients (13 women) were using these drugs to treat insomnia related to pain. The mean visual analogue pain score for night pain showed a significant difference between those receiving night sedation (5.2) and those who were not (3.7). Of the 70 patients who answered the Stanford Health Assessment Questionnaire (HAQ), those receiving night sedation also had a significantly higher mean score (1.91) than those who were not (1.2), suggesting that patients receiving night sedation were more clinically disabled. Codeine was used by more (34%) patients receiving night sedation than those who were not (18%) suggesting that those receiving night sedation had more pain. These results highlight the need for better pain management in patients with rheumatic diseases to minimise the risk of prescribing addictive drugs such as hypnotic drugs and codeine.


Repetitive strain disorder: towards diagnostic criteria. Thirteen women (mean age 48.2 years; range 25-60 years) all of whom had developed musculoskeletal symptoms during employment in an industrial job with repetitive tasks were referred by their trade unions for adjudication on the cause of symptoms. One had rheumatoid arthritis. A study of the other 12 women provided an opportunity to document the natural history of repetitive strain disorder. Early symptoms of weakness were diffuse but were always relieved by rest. Several months later localisation of symptoms at a tendon, nerve, or enthesis could be predicted from the analysis of the action required in the particular repetitive task. Six of the 12 women required an operation several years later, thus providing histological confirmation of the presence of a lesion. Early loss of grip strength measured by a sphygmomanometer cuff compared with an unaffected control subject and improved by rest may be the most valuable sign in excluding compensation neurosis. The estimated prevalence of repetitive strain disorder defined by these strict criteria was at least 2% in conveyor belt workers.


Detection of cytokine activated chondrocytes in arthritic joints from pigs infected with Erysipelothrix rhusiopathiae. Chronic polyarthritis was induced in pigs by injection of Erysipelothrix rhusiopathiae and the in vivo activation of chondrocytes by cytokines was then investigated in the affected joints by immunocytochemistry. A polyclonal antiserum which recognises surface markers on in vitro interleukin 1 activated porcine chondrocytes was used to detect activated chondrocytes in all zones of the cartilage from diseased joints. In contrast, cartilage removed from an unaffected joint in the same animal showed no chondrocyte activation. Inflammatory synovial tissue removed from diseased joints and cocultured with cartilage from the unaffected joint induced activation of adjacent chondrocytes. The presence of interleukin 1 in the inflammatory cells of the synovium was confirmed and major histocompatibility complex (MHC) class II antigens were detected as a marker of synovial activation. Chondrocytes were found not to express class II antigens in cartilage from either the diseased or the unaffected joint. These observations show that the porcine erysipelas model of arthritis will be useful in facilitating a novel approach to monitoring the behaviour of individual chondrocytes under pathophysiological conditions.


Dependence of proteoglycan induced arthritis in BALB/c mice on the development of autoantibodies to high density proteoglycans. BALB/c mice were immunised with high or low density native human cartilage proteoglycans, or the respective core proteins obtained from chondroitin ABC lyase digestion. Mice injected with high density native proteoglycans developed arthritis whereas mice injected with low density proteoglycans or with core proteins did not. Analysis of the immune response by enzyme linked immunosorbent assay (ELISA) and western blot showed a stronger and more polyspecific response in animals injected with low density proteoglycans compared with mice with arthritis which had been injected with high density proteoglycans. Autoantibodies to mouse high density proteoglycans were only present in mice injected with native human high density proteoglycans, however. The data suggest that an arthritogenic epitope lies within the glycosaminoglycan rich region of the native proteoglycan molecule, which may induce an autoantibody response and subsequently arthritis in BALB/c mice.


Uridine diphosphoglucose dehydrogenase activity in synovial lining cells in the experimental antigen induced model of rheumatoid arthritis: an indication of synovial lining cell function. Uridine diphosphoglucose dehydrogenase (UDPGD) is the enzyme responsible for the production of uridine diphospho(UDP)-glucuronate, an essential monosaccharide in the biosynthesis of hyaluronan, which is found in high concentrations in normal synovial fluid. Synovial lining cells have been implicated in the synthesis of hyaluronan, but the degree to which they are adapted metabolically to this function in normal and inflamed synovium has not been established. Using a quantitative cytochemical method it was shown that synovial lining cells from chronically inflamed rabbit synovium had significantly lower UDPGD activity per cell than the lining cells of normal synovium. These findings suggest that the lining cells of normal non-inflamed synovium may be enzymatically adapted for the synthesis of hyaluronan and that this may be an indication of a specific role of synovial lining cells in the maintenance of normal joint function.


Remission of scleroderma during chemotherapy for lymphoma. Temporary remission of scleroderma during the successful treatment of an associated malignant lymphoma by chemotherapy is reported in a patient with systemic sclerosis and mixed connective tissue disease. There is a well established relation between malignant disease and polymyositis/dermatomyositis but no overall association with systemic sclerosis or mixed connective tissue disease. Reports of the coexistence of malignancy and systemic sclerosis, however, emphasise a close temporal relation in their occurrence. A review of published work has identified several postulated mechanisms for this relation which may explain the response to chemotherapy.


Clinical significance of rheumatoid factors in early rheumatoid arthritis: results of a follow up study. Serum rheumatoid factors (RF) were measured yearly in 135 women with rheumatoid arthritis by the Waaler-Rose and latex fixation tests and IgM, IgA, and IgG RF were measured by enzyme linked immunosorbent assays (ELISAs). The patients were followed up from an early phase of the disease for a mean duration of six years. Patients with a persistently positive RF test, irrespective of the type of test used, had more radiological abnormalities, more disease activity, worse functional ability, more extra-articular manifestations, and needed more treatment with second line drugs than patients with persistently negative or variably positive and negative test results during the follow up. Increased RF levels, especially a high level of IgA RF within three years of the onset of symptoms, was prognostic for a more severe disease outcome six years after the onset of symptoms.


Decreased level of antibodies against Helicobacter pylori in patients with rheumatoid arthritis receiving intramuscular gold. Sodium aurothiomalate has been reported to have in vitro activity against Helicobacter pylori. Intramuscular gold, as given to patients with rheumatoid arthritis (RA), may therefore influence the colonisation of the gastric mucosa with H pylori. Two groups were compared. One group of 42 patients was treated with intramuscular gold; the other group of 58 patients was treated with antimalarial drugs. Antibodies to H pylori (IgA and IgG) were assessed by an enzyme linked immunosorbent assay (ELISA) and total IgA and IgG were measured by nephelometry. IgA and IgG antibody titres against H pylori and total IgA and IgG levels were lower in the patients treated with gold than in the group treated with antimalarial drugs. The ratio of IgA antibodies to H pylori to total IgA antibodies and the ratio of IgG antibodies to H pylori to total IgG antibodies were lower in the group treated with gold. The percentage of seropositivity to H pylori was significantly lower in the group treated with gold than in the group treated with antimalarial drugs for the two IgA antibodies (35 and 55% respectively) and IgG antibodies to H pylori (40 and 65% respectively). Although this study cannot completely exclude the possibility that a suppressive effect of intramuscular gold on total immunoglobulin production plays a part in the decrease in the titres of IgA antibodies to H pylori and IgG antibodies to H pylori, the lower ratios of antibodies to H pylori to total immunoglobulin antibodies and the lower percentages of seropositivity to H pylori in the group treated with gold suggests that treatment with intramuscular gold decreases H pylori colonisation.


Recombinant human interferon gamma in the treatment of rheumatoid arthritis: double blind placebo controlled study. Interferon gamma (IFN gamma) has been advocated in open studies as a beneficial remission inducing drug for the treatment of rheumatoid arthritis (RA). The work reported here was designed to assess the therapeutic potential of IFN gamma in the treatment of RA in a double blind placebo controlled study. It was found that patients treated with IFN gamma improved significantly with respect to morning stiffness, grip strength, swelling of an index joint, and erythrocyte sedimentation rate. Furthermore significantly more responders (according to predetermined response criteria) were found in the group treated with IFN gamma. Only minor adverse effects and no significant toxicity with respect to clinical or laboratory parameters were observed.


Glutathione redox cycle enzymes and selenium in severe rheumatoid arthritis: lack of antioxidative response to selenium supplementation in polymorphonuclear leucocytes. The antioxidant capacity of the glutathione redox cycle and the concentrations of selenium in serum, red blood cells or whole blood, and polymorphonuclear leucocytes was evaluated in nine patients with severe rheumatoid arthritis (RA) and eight healthy controls receiving daily supplementation with 250 micrograms selenomethionine for six months. Serum and whole blood concentrations of selenium and the activity of the selenium dependent enzyme glutathione peroxidase (GSH-Px) were low in the serum, red blood cells, and polymorphonuclear leucocytes of patients with RA before selenium supplementation. During supplementation serum and whole blood concentrations of selenium and the activity of GSH-Px in serum and red blood cells of patients with RA and serum GSH-Px in controls increased. Selenium and GSH-Px in polymorphonuclear leucocytes were unaffected in patients with RA in contrast with the controls where both were augmented. Glutathione reductase activity in the red blood cells and polymorphonuclear leucocytes of patients with RA was low but increased during selenium supplementation. Whole blood concentrations of glutathione were slightly lower in patients with RA than controls and no difference in the content in polymorphonuclear leucocytes was found between the groups. The activity in red blood cells of glucose-6-phosphate dehydrogenase was high in patients with RA, indicating sufficient function of the hexose monophosphate pathway. The reduced antioxidant activity of the glutathione redox cycle in patients with severe RA was mainly due to the low availability of selenium. This was further supported by the response to selenium supplementation in serum and red blood cells. In the polymorphonuclear leucocytes, however, no biochemical effects of selenium supplementation were seen. This lack of antioxidative response could play a pathogenetic part in inflammation in patients with RA.


Systemic lupus erythematosus in men: clinical and immunological characteristics. Although systemic lupus erythematosus (SLE) has traditionally been considered a disease of women, men may also be affected. Thirty of 261 patients (12%) with SLE seen in this hospital were men. Arthritis was less common as a first symptom in the men, although this group of patients had discoid lesions and serositis more often than the women. During the follow up a lower incidence of arthritis and malar rash and a higher incidence of other skin complications including discoid lesions and subcutaneous lupus erythematosus was found in the men. The incidence of nephropathy, neurological disease, thrombocytopenia, vasculitis, and serositis, was similar in the two groups. No significant immunological differences were found between men and women. These features indicate that several gender associated clinical differences may be present in patients with SLE.


Correlation of antibodies to ribosomal P protein with psychosis in patients with systemic lupus erythematosus. Ninety one Japanese patients with systemic lupus erythematosus (SLE) were studied to determine the clinical significance of antibodies to ribosomal P protein (anti-P). Anti-P was detected by western blotting in 38 of 91 patients (42%). Clinical symptoms of SLE were compared between patients with and without anti-P. The occurrence of lupus psychosis was significantly higher in patients with anti-P than in those without anti-P (9/38 v 1/53). No significant association was found between anti-P and other symptoms of SLE. These data strongly support the suggestion proposed by previous workers that anti-P is a marker autoantibody for the development of lupus psychosis.


Preliminary observations of chondral abrasion in a canine model. Articular cartilage repair was followed for one year in skeletally mature dogs after destabilisation by anterior cruciate ligament transection of the stifle joint (CT), abrasion of the inferior medial condyle (ABR) to bleeding bone, or anterior cruciate transection followed by chondral abrasion (CT/ABR). ABR animals formed repair cartilage at the abrasion site (ABR and CT/ABR) at six months as determined by arthroscopy and at necropsy. CT and CT/ABR animals had an additional cartilage ulcer on the superior aspect of the medial condyle. The abraded site extended in CT/ABR condyles. Repair cartilage (ABR and CT/ABR) contained reduced amounts of proteoglycan as seen by histological loss of safranin O staining and reduced uronic acid content. Fibrocartilage was suggested by histological appearance, hypocellularity, and a higher hydroxyproline content. In contrast with ABR animals, the repair cartilage in the CT/ABR animals contained near normal amounts of hydroxyproline. Collagen profiles of abrasion site repair cartilage in ABR animals had more types I and V collagens, similar amounts of type VI collagen, and decreased amounts of types II, IX, and XI collagens than CT/ABR animals. The results of this study are consistent with abrasion chondroplasty leading to a repair cartilage. Despite extended ulcers, repair cartilage from the destabilised joint (CT/ABR) animals was more hyaline-like in its hydroxyproline content and collagen composition than repair cartilage from the stable joint (ABR animals). In these models additional measures appear to be needed as the defects induced by abrasion chondroplasty did not form a functional hyaline cartilage.


Fracture thresholds in osteoporosis: implications for hormone replacement treatment. The bone mineral densities of the lumbar spine and femoral neck were determined by dual energy chi ray absorptiometry in 110 women aged 40-82 years (average 65 years) with spinal osteoporosis who had had at least one atraumatic vertebral compression fracture and in 1026 normal women aged 40-79 years (average 52 years). The women with osteoporosis showed a significant decrease in bone mineral density (BMD) at the lumbar spine and femoral neck compared with age matched normal women (sixth decade of life -26% spine, -23% femoral neck; seventh decade -26% spine, -16% femoral neck). The fracture threshold, defined as the 90th centile of spinal BMD for women with osteoporosis, was 0.81 g/cm2 at the lumbar spine and 0.656 g/cm2 at the femoral neck. Five per cent of normal women aged 40-49 years, 20% aged 50-59 years, and 45% aged 60-69 years had a BMD below this threshold. To maintain the bones of women above the fracture threshold until the age of 70 years about 50% of postmenopausal women need hormone replacement therapy. However, if the BMD is to be kept above the fracture threshold for a women's lifetime, e.g. until the age of 80-90 years, then most women will need treatment, though for various lengths of time depending on their initial BMD. Measurements of BMD in postmenopausal women currently help in identifying the risk of osteoporotic fractures but in the lifetime assessment of risk in a single subject they may have a more important role in deciding the duration of hormone replacement therapy.


Differential involvement of the dorsal and lumbar spine in osteoporosis. The presence of normal bone density values in the lumbar spine is often assumed to exclude osteoporosis. Eleven cases are reported in which normal lumbar spine bone density and radiology were associated with one or more dorsal spine fractures; the diagnosis was postmenopausal osteoporosis in eight patients and corticosteroid induced osteoporosis in three. These findings suggest that spinal osteoporosis may sometimes be a focal disorder and emphasise the need for dorsal spine radiology in addition to bone densitometry in patients with strong risk factors for osteoporosis or with clinical evidence of the dorsal spine being affected.


False positive results for antibody to HIV in two men with systemic lupus erythematosus. False positive results were obtained for HIV tests in two men with active systemic lupus erythematosus (SLE) who were suspected of being infected with HIV because of fever, weight loss, lymphadenopathy, and inflammatory myopathy. Enzyme linked immunosorbent assays (ELISAs) for HIV were twice positive when tested three times over a period of six months. Western blot analysis showed reactivity against the gp41 band in patient 1. False positive results for HIV tests can occur in patients with SLE, potentially leading to an erroneous diagnosis of HIV infection.


Mycotic aneurysm of the aortic arch masquerading as systemic lupus erythematosus. The case is described of a patient with mycotic aneurysm of the aortic arch whose clinical and serological features were indistinguishable from those of systemic lupus erythematosus. Surgical resection and repair of the aneurysm resolved her clinical symptoms and the serological abnormalities.


Primary idiopathic osteolysis: description of a family. A clinical, analytical, and radiological study was carried out on three members of the same family with multicentric idiopathic osteolysis. Transmission appeared to be via the dominant autosome present in the mother and two daughters. In the daughters osteolysis was seen in the carpal and tarsal bones, whereas in the mother radiology showed it to be in the phalanges of the hands and feet.


Temporal arteritis: a form of systemic panarteritis. The case is reported of a patient with giant cell arteritis affecting several organs. The triggering cause of death was a brainstem infarction due to basilar artery thrombosis. The necropsy showed the systemic character of the disease affecting the coronary, bronchial, and ovarian arteries.


Systemic lupus erythematosus induced by isoniazid. The case is described of a 73 year old man who presented with a lupus-like syndrome related to treatment with isoniazid and had IgG antinuclear antibodies against the nucleo-histone complex (H2A-H2B)-DNA. After a short course of treatment with prednisone and discontinuation of isoniazid the patient's lupus symptoms resolved and a gradual decrease in antibodies to (H2A-H2B)-DNA occurred. This case suggests that isoniazid is capable of inducing an autoantibody specificity associated with drug related lupus.


Misoprostol in the prevention of gastroduodenal damage in rheumatology. Patients receiving non-steroidal anti-inflammatory drugs (NSAIDs) are at an increased risk of gastroduodenal erosions, ulcers, and the associated complications of haemorrhage, perforation, and death. Many NSAID associated ulcers that bleed or perforate have been asymptomatic until the time of presentation and conversely many patients with dyspepsia do not have ulcers. Symptoms are a poor guide to the presence of an ulcer. During continued treatment with NSAIDs misoprostol is the best choice for NSAID induced gastroduodenal damage; it achieves higher rates of healing than other drugs in these circumstances. Misoprostol is superior to other drugs in the prevention of gastric damage but misoprostol and H2 antagonists are of similar benefit in the duodenum. Prophylactic studies have all used endoscopic damage as an endpoint, and much larger studies will be needed to show an effect of misoprostol on the incidence of ulcer complications. There are no clear guidelines as to which patients should receive prophylactic treatment with misoprostol but those particularly at risk of ulcer complications--that is, those with previous peptic ulceration, the elderly, medically unfit, patients receiving large doses of NSAIDs, and those patients receiving steroids in addition to NSAIDs--should be considered.


[Evaluation of the efficacy of fenitrothion (Sumithion PM40) on vector density and the prevalence of malaria in Pout (Thiès, Sénégal)]. House-spraying with fenitrothion for malaria control was evaluated in three villages of the Pout rural community (Senegal) between August 1988 and October 1990. The baseline data were collected during the first year. The malaria vector was identified as Anopheles arabiensis and the highest malaria prevalence was observed in October 1988 (38%) in the child population (2-9 years old). A simple round of fenitrothion house-spraying at 1 g/m2 was carried out in the second part of July 1989. About 90% of the houses were treated. The malaria vector was reduced to negligible density and a rapid decrease of malaria prevalence was observed. In this area of short seasonal transmission, where the stability of malaria is low, one single round of spraying led to a marked reduction of malaria transmission and prevalence. The cost of the treatment was about 50 US cents per capita.


[Serological evidence of the existence of a wild reservoir of Trypanosoma brucei gambiense in the Pendjari biosphere reservation in the Republic of Benin]. In the national park of Pendjari, situated in the North-West of Benin, 91 wild animals, belonging to seven species, were darted. Thick and thin blood smears were examined for trypanosomes and plasma for trypanolytic antibodies against 6 antigenic variants of Trypanosoma brucei gambiense. Parasites were found in 13.92% and trypanolytic antibodies in 20.88% of the samples. A total of 28.57% of animals were positive by at least one of the two test systems used. Morphologically Trypanosoma congolense, T. vivax and T. brucei were identified. Overall prevalence was 40% in Adenota kob (n: 50), 13.63% in Alcelaphus buselaphus (n: 22), 10% in Hippotragus equinus (n: 10), 33% in Kobus defassa (n: 3), 0% in Phacochoerus aethiopicus (n: 3) and in Syncerus caffer (n: 2). The only lion (Panthera leo) examined was serologically positive. The results indicate that the wild animals are reservoirs of animal trypanosomes and suggest that among them Adenota kob and Panthera leo are carriers of T. brucei gambiense, one of the etiological aspects of human trypanosomiasis.


[Ivermectin or diethylcarbamazine in spaced dosages in Bancroft's filariasis: which protocol?]. 58 apparently healthy Polynesian Wuchereria bancrofti carriers were randomly allocated to 5 treatment groups: 1) two annual doses of ivermectin 100 mcg/kg, 2) three semi-annual doses of ivermectin 100 mcg/kg, 3) two annual doses of diethylcarbamazine (DEC) 3 mg/kg, 4) semi-annual doses of DEC 3 mg/kg, 5) two annual doses of DEC 6 mg/kg. Results observed during the 12-month period which followed last treatment have confirmed that efficacy of ivermectin is higher than that of DEC in terms of immediate clearance or complete negativation of microfilaremia, but not in terms of sustained reduction and that efficacy of repeated single doses of either DEC 3 mg/kg or ivermectin 100 mcg/kg is much higher when given semi-annually than annually. They also have indicated that (i) 6 months after last treatment: 3 semi-annual doses of 100 mcg/kg of ivermectin have resulted in high reduction of microfilaremia (85%) and, 2 annual doses of 6 mg/kg and 3 semi-annual doses of 3 mg/kg of DEC have resulted in even greater reduction (96 and 98% respectively) and (ii): 12 months after last treatment, the greatest reductions of microfilaremia (95 and 92%) have been observed in carriers treated, respectively, with 3 semi-annual doses of 3 mg/kg or with 2 annual doses of 6 mg/kg of DEC.(ABSTRACT TRUNCATED AT 250 WORDS)


HIV screening and confirmation: a simplified and less expensive testing algorithm. In this study we investigated the performance of fourteen different assays capable of simultaneously detecting antibodies to HIV-1 and HIV-2, referred to as combined screening assays (CSAs), on a panel of 371 sera, with a prevalence of 51.5% and 1.3% for HIV-1 and HIV-2 antibodies respectively. The geographic distribution of the sera was as follows; Europe (121), Africa (203) and Latin America (47). These sera were collected from different clinical groups of patients; Asymptomatic (36), AIDS-Related Complex/AIDS patients (18), infected individuals with generalised lymphadenopathy (12), blood donors (149), and subjects with unknown clinical status (156). The Dupont Western blot (WB) kit for detection of HTLV-III antibodies and the Pasteur new Lav-Blot II kit were used for the confirmation of HIV-1 and HIV-2 infection respectively. Of the 14 tests studied, 9 were enzyme linked immunosorbent assays (ELISAs), and 5 were non-Elisa tests requiring visual reading. An alternative approach for HIV antibody testing was studied restrospectively, whereby sera positive in an initial CSA (A) were retested on a second CSA (B), that was different from the first. The use of WB was limited to sera that gave discrepant (A+B-) results in the two CSAs. A positive result in both CSAs was reported as anti-HIV positive. A negative result in the first CSA was reported anti-HIV negative. Sensitivity, specificity, cost, and the delta (delta) values (delta values of the ELISA assays) were taken into consideration when selecting suitable pairs of assays. All the ELISAs scored 100% sensitivity, but for the non-ELISAs, the sensitivity ranged from 96.0% to 100%. The specificity for the ELISAs and non-ELISAs varied from 87.4% to 100% and from 51.4% to 100% respectively. Delta (delta) values for the ELISAs ranged from 3.82 to 136.68 and from -1.15 to -3.08 for the anti-HIV positive and anti-HIV negative populations respectively. Of the 121 test combinations studied, 9 (7.4%) pairs yielded 100% sensitivity and specificity and 61 (50.4%) pairs of CSAs required further testing on WB. This implies 100% positive predictive value, at a cost that was on average 6 times less, and a testing time that was 5 times faster than the conventional algorithm. We conclude that there are several combinations of pairs of CSAs that can be used in the alternative algorithm that can provide accurate results at a much lower cost than the conventional algorithm requiring confirmation by WB of all initially reactive CSA results.(ABSTRACT TRUNCATED AT 400 WORDS)


[Community health workers are capable of determining reliably the target population for health programs]. The target population is a key concept for the planning and evaluation of health services. However, in developing countries, health professionals in the field are often uneasy with the determination of the population denominator. In Zaire, where reliable demographic data are hardly available, we make use of two different methods aimed to the determination of the size of the target population: (1) an exhaustive population based survey performed by trained interviewers, and (2) a rapid census of the target population performed by community health workers. This paper presents both the results of a demographic survey organized in 1984, and two consecutive census performed by community health workers in 1986 an 1988, in the same area (Northern-Kivu, Zaire). Our results suggest that community health workers under close supervision are able to perform rapidly and at low cost a reliable collection of the demographic data needed for the implementation and monitoring of health programmes at the local level.


[The severity of a snake bite. Apropos of 3 case reports in the Congo]. Three observations of sanke-bite that occurred in the Congo are reported: the bite of an aglyph colubridae (Philothamnus nitidus loveridgee) that was severe; the bite of an Atheris s.p. with moderate symptoms; the bite of a Naja melanoleuca remained totally asymptomatic.


Kashin-Beck disease.

Kashin-Beck disease. The article describes the history, clinical picture and anatomopathological changes of Kashin-Beck disease with reference to the stages of the disease which are at present agreed upon. Specific reference is made to the occurrence of the disease in Tibet. An overview is given of the different proposed etiologies.


Only the serum-resistant bloodstream forms of Trypanosoma brucei rhodesiense express the serum resistance associated (SRA) protein. The Trypanosoma brucei species consists of three subspecies. T. b. rhodesiense and T. b. gambiense are human infective forms, while T. b. brucei is lysed upon exposure to the cytotoxic factor in normal human serum. T. b. rhodesiense can however occur as a serum-resistant (R) and as a serum-sensitive form (S). In a study of the molecular basis of serum resistance in T. b. rhodesiense it was shown that in the cloned ETaR1-repertoire only the serum-resistant variants express specific transcripts, encoding a protein with VSG-characteristics. When a serial of freshly isolated T. b. rhodesiense isolates was tested, the presence of the R-transcripts in the serum-resistant populations was confirmed. The absence of the serum resistance associated (SRA) mRNAs in several isolates from T. b. brucei and especially T. b. gambiense (including an a-typical one), indicates that more than one mechanism might be involved in the phenomenon of serum resistance in the T. brucei group. Neither T. evansi, nor T. equiperdum expresses the SRA-transcripts. Interestingly, the transcription of the R-specific transcripts is not maintained during the life cycle of T. b. rhodesiense; in the procyclic forms the SRA-mRNAs are no longer present.


Mechanisms underlying trypanosome-elicited immunosuppression. T-cell proliferative responses of lymph node cells are profoundly suppressed during experimental infections of mice with Trypanosoma brucei. The active suppression of lymph node T-cell proliferative responses is attributed to the coexistence of at least two unlinked suppressive mechanisms that block different T-cell regulatory steps and operate through different effector mechanisms. The generation of prostaglandin-producing macrophages is entirely responsible for the suppression of IL-2 production whereas the induction of a prostaglandin-independent suppressive mechanism accounts for the suppression of the expression of IL-2 receptors (IL-2R). Both mechanisms are mediated by the cells that co-purify which macrophages. Despite an impairment at the level of T-cell proliferation, lymph node cells from T. brucei infected animals produce substantial amounts of interferon-gamma (IFN-gamma) and this lymphokine participates in the down-regulation of IL-2R expression. T-brucei-pulsed macrophage cell lines acquire concomitantly the potential to suppress T-cell proliferative responses and to stimulate CD8+ T-cells to secrete IFN-gamma. The sensibilization of CD8+ T cells by T. brucei-pulsed macrophages might be mediated by TNF-alpha. Collectively, these results indicate that the uptake of T. brucei by macrophages, either in vivo or in vitro, results in the generation of suppressive cells that annihilate T-cell proliferative responses. Furthermore, at least two cytokines (i.e., TNF-alpha and IFN-gamma) are released during these interactions. Besides playing a role in the pathway of T-cell immunosuppression, TNF-alpha and IFN-gamma could also contribute to immunopathological features that occur during trypanosome infections.


Advances in sleeping sickness therapy.

Advances in sleeping sickness therapy. The efficacy and adverse effects of nifurtimox and DFMO in the treatment of sleeping sickness are reviewed. Both new substances constitute effective novel therapeutic agents for gambiense sleeping sickness, including melarsoprol-refractory disease. DFMO is not very active in rhodesiense sleeping sickness and experience with nifurtimox in this form of trypanosomiasis is too limited to draw valid conclusions. The toxicity of nifurtimox and DFMO is not negligible. Optimum dosage and duration of therapy, modes of administration and potential for large scale use are discussed. Some recent results obtained with the classical trypanocide melarsoprol are presented to facilitate comparison. The current availability of several effective late-stage drugs (melarsoprol, nifurtimox and DFMO), that show synergistic activity in experimental models, should allow the establishment of optimum combination treatment regimens.


Effect of intraportal glucose infusion on hepatic glycogen content and degradation, and outcome of liver transplantation. Recent animal studies suggest that nutritional repletion may improve function of liver allografts, and the authors have found that intraportal glucose infusion in pigs produces rapid and substantial hepatic glycogenation. A controlled prospective randomized study in 32 patients was done to determine glycogen content and degradation in human livers during transplantation, and the effect of intraportal glucose-insulin infusions during the donor operation on these variables and on outcome of transplantation. Peripheral blood glucose concentrations were "clamped" at 14 mmol/L during the glucose-insulin infusion. Liver biopsies were taken at various stages of the procedure. Liver glycogen decreased 2.0 +/- 1.2 g/100 g dry weight liver (mean +/- standard error of the mean) in controls, but increased 6.8 +/- 1.8 g/100 g dry weight in glucose-infused donors. In both groups there was glycogen degradation during periods of cold preservation, anoxic rewarming, and after reperfusion with portal blood. Degradation rates were greater in the glucose-infused group than in controls in all three periods (p less than 0.05). Despite wide variation in postoperative aspartate aminotransferase (AST) levels among recipients in both groups, the difference in peak postoperative AST levels approached significance (p = 0.06). In addition, peak AST levels were closely correlated to anoxic rewarming time in both groups, but the slope of the relationship was much lower (3834 versus 734, p less than 0.01) in the glucose-infused group. Thus at anoxic rewarming times over 90 minutes, glycogenation was protective of liver function. Peak postoperative AST was significantly correlated to glycogen degradation in the cold preservation and rewarming periods in the glucose-infused group only. Intraoperative glucose infusions in humans can reglycogenate the liver, increase glycogen degradation, and improve certain outcome measures in liver transplantation.


Selective shunt in the management of variceal bleeding in the era of liver transplantation. This study reports the Emory experience with 147 distal splenorenal shunts (DSRS) and 110 orthotopic liver transplants (OLT) between January 1987 and December 1991. The purpose was to clarify which patients with variceal bleeding should be treated by DSRS versus OLT. Distal splenorenal shunts were selected for patients with adequate or good liver function. Orthotopic liver transplant was offered to patients with end-stage liver disease who fulfilled other selection criteria. The DSRS group comprised 71 Child's A, 70 Child's B, and 6 Child's C patients. The mean galactose elimination capacity for all DSRS patients was 330 +/- 98 mg/minute, which was significantly (p less than 0.01) above the galactose elimination capacity of 237 +/- 82 mg/minute in the OLT group. Survival analysis for the DSRS group showed 91% 1-year and 77% 3-year survival, which was better than the 74% 1-year and 60% 3-year survivals in the OLT group. Variceal bleeding as a major component of end-stage disease leading to OLT had significantly (p less than 0.05) poorer survival (50%) at 1 year compared with patients without variceal bleeding (80%). Hepatic function was maintained after DSRS, as measured by serum albumin and prothrombin time, but galactose elimination capacity decreased significantly (p less than 0.05) to 298 +/- 97 mg/minute. Quality of life, measured by a self-assessment questionnaire, was not significantly different in the DSRS and OLT groups. Hospital charges were significantly higher for OLT (median, $113,733) compared with DSRS ($32,674). These data support a role for selective shunt in the management of patients with variceal bleeding who require surgery and have good hepatic function. Transplantation should be reserved for patients with end-stage liver disease. A thorough evaluation, including tests of liver function, help in selection of the most appropriate therapeutic approach.


Is portal-systemic shunt worthwhile in Child's class C cirrhosis? Long-term results of emergency shunt in 94 patients with bleeding varices. A prospective evaluation was conducted of 94 unselected patients ("all comers") with biopsy-proven Child's class C cirrhosis (93% alcoholic) and endoscopically proven acutely bleeding esophageal varices who underwent emergency portacaval shunt (EPCS) (85% side-to-side, 15% end-to-side) within 8 hours of initial contact (mean, 6.1 hours) during the past 12 years. Follow-up has been 100% and includes all patients for at least 1 year, and 61 patients (65%) for 5 to 12 years. Incidence of serious risk factors on initial contact was: ascites, 97%; jaundice, 86%; portal-systemic encephalopathy including past history, 71%; severe muscle wasting, 96%; alcohol ingestion within 7 days, 66%; delirium tremens, 16%; serum albumin, less than or equal to 2.5 g/dL 76%; indocyanine green dye retention greater than or equal to 50% in 45 minutes, 66%; serum glutamic-oxaloacetic transaminase greater than or equal to 100 units/L, 60%; hyperdynamic cardiac output greater than or equal to 6 L/minute, 98%. Mean Child's point score was 13.7 out of a maximum of 15. EPCS reduced mean corrected free portal pressure from 286 to 23 mm saline, and permanently controlled variceal bleeding in every patient. Of the 94 patients, 74 (80%) left the hospital alive and 68 (72%) survived 1 year. Five-year actuarial survival rate is 64%. Hepatic failure was the main cause of death during initial hospitalization as well as during follow-up, when it was related to continued alcoholism. Portal-systemic encephalopathy, which was present on initial contact in 55% of patients, occurred at some time during follow-up in 18.7%, but was recurrent and required dietary protein restriction in only 9%, all of whom had resumed alcoholism. The low incidence of portal-systemic encephalopathy was attributable to the lifelong program of follow-up with regular dietary counseling and continued emphasis on both protein restriction to 60 g/day and abstinence from alcohol. Abstinence was sustained in 69%, liver function improved in 82%, general health was judged excellent or good in 73%, and Child's risk class converted to class B in 73% and class A in 21%. Excluding retirees because of age, 42% were gainfully employed or engaged in full-time housekeeping. Long-term shunt patency was documented in 100% of survivors by yearly angiography or Doppler ultrasonography. It is concluded that EPCS within 8 hours of initial contact permanently controls variceal hemorrhage and results in prolonged survival and a life of acceptable quality in many alcoholic cirrhotic patients in Child's class C.(ABSTRACT TRUNCATED AT 400 WORDS)


Results of surgery on 6589 gastric cancer patients and immunochemosurgery as the best treatment of advanced gastric cancer. Results of 6589 gastric cancer operations at the Department of Surgery, Seoul National University Hospital, from 1970 to 1990 were reported. About two thirds (76.6%) were advanced gastric cancer (stages III and IV). The 5-year survival rate of operated stage III gastric cancer was only 30.6%, with frequent recurrence. Conversely, cell-mediated immunities of advanced gastric cancer patients were significantly decreased. Therefore, to improve the cure rate and to prevent or delay recurrence, curative surgery with confirmation of free resection margins and systematic lymph node dissection of perigastric vessels were performed and followed by early postoperative immunotherapy and chemotherapy (immunochemosurgery) in stage III patients. To evaluate the effect of immunochemosurgery, two randomized trials were studied in 1976 and 1981. In first trial, 5-fluorouracil, mitomycin C, and cytosine arabinoside for chemotherapy and OK 432 for immunotherapy were used. The 5-year survival rates for surgery alone (n = 64) and immunochemosurgery (n = 73) were 23.4% and 44.6%, respectively, a significant difference. In the second trial, there were three groups: group I, immunochemosurgery (n = 159); group II, surgery and chemotherapy (n = 77); and group III, surgery alone (n = 94). 5-Fluorouracil and mitomycin C for chemotherapy and OK-432 for immunotherapy were administered for 2 years. The 5-year survival rate of group I was 45.3%, significantly higher than the 29.8% of group II and than the 24.4% of group III. The postoperative 1-chloro-2.4-dinitrobenzene test, T-lymphocyte percentage, phytohemagglutinin- and con-A-stimulated lymphoblastogenesis and the antibody-dependent cell-mediated cytotoxicity test showed more favorable values in the immunochemosurgery group. Therefore, immunochemosurgery is the best multimodality treatment for advanced gastric cancer.


Growth hormone and insulin reverse net whole body and skeletal muscle protein catabolism in cancer patients. The authors examined the effect of recombinant-human growth hormone (r-hGH) and insulin (INS) administration on protein kinetics in cancer patients. Twenty-eight cancer patients either received r-hGH for 3 days (GH group, n = 12, weight loss = 6 +/- 2%) or were not treated (control [CTL] group, n = 16, weight loss = 11 +/- 2%) before metabolic study. Recombinant-human growth hormone dose was 0.1 mg/kg/day (n = 6) or 0.2 mg/kg/day (n = 6). Patients then underwent measurement of baseline protein kinetics (GH/B, CTL/B) followed by a 2-hour euglycemic insulin infusion (1 mU/kg/minute) and repeat kinetic measurements (GH/INS,CTL/INS). Whole-body protein net balance (mumol leucine/kg/minute) was higher (p less than 0.05) in GH/INS (0.20 +/- 0.06) than in CTL/INS (0.06 +/- 0.03) or GH/B (-0.19 +/- 0.03). Skeletal muscle protein net balance (nmol phenylalanine/100 g/minute) in GH/INS (25 +/- 6) and CTL/INS (19 +/- 5) was higher than CTL/B (-18 +/- 3). Recombinant-human growth hormone and insulin reduce whole-body and skeletal muscle protein loss in cancer patients. Simultaneous use of these agents during nutritional therapy may benefit the cancer patient.


Thoracoscopic esophagomyotomy. Initial experience with a new approach for the treatment of achalasia. The authors treated 17 patients with achalasia by a thoracoscopic (15 patients) or laparoscopic (2 patients) Heller myotomy. All patients had dysphagia and an upper gastrointestinal series demonstrating a dilated esophagus with a bird-beak deformity at the cardia. Manometry showed a mean lower esophageal sphincter (LES) pressure of 32 +/- 4 mmHg, incomplete sphincter relaxation on swallowing, and no primary esophageal peristalsis. After operation, mean LES pressure was 10 +/- 2 mmHg. Fifteen patients were fed on the second postoperative day. The average hospital stay was 3 days, and there were no deaths or major complications. In three early patients, the myotomy was not carried far enough onto the stomach, and dysphagia persisted until a second myotomy was performed (laparoscopically in two patients). The authors found that having an endoscope in the esophagus during the operation facilitated exposure and was vital to determine the appropriate length of the myotomy. With regard to dysphagia, final results were excellent in 12 patients (70%), good in two patients (12%), fair in two patients (12%), and poor in one patient (6%). Heller myotomy can be safely and reliably performed with minimally invasive techniques. Dysphagia is relieved, postoperative pain is minimal, hospital stay is short, and the patient can return quickly to normal activity.


Transforming growth factor (TGF)-beta stimulates hepatic jun-B and fos-B proto-oncogenes and decreases albumin mRNA. Transforming growth factor-beta (TGF-beta) modulates some components of the acute phase response in hepatic cells. The mechanisms for these actions of TGF-beta are largely unknown. The authors recently found that the decrease in albumin mRNA after TGF-beta 1 treatment required de novo RNA and protein synthesis, suggesting that TGF-beta acts through induction of another gene. The purpose of the current study was to determine whether TGF-beta 1 could regulate the expression of both the jun and fos genes that encode transcriptional regulatory proteins that constitute the AP-1 complex, and to determine whether expression of these genes may be coordinated with the decrease in albumin mRNA. Northern blot hybridization was used to determine levels of specific mRNAs. Transforming growth factor-beta 1 increased the levels of both jun-B and fos-B mRNA by 60 minutes after treatment of mouse hepatoma (BWTG3) cells. When TGF-beta 1 was removed from the media after 4 hours, there was a sustained effect of increased jun-B and decreased albumin mRNA (greater than 48 hours), and the subsequent decrease in jun-B levels coincided with the increase in albumin mRNA. The tumor-promoting phorbol ester (phorbol 12-myristate 13-acetate [PMA]), known to induce jun and fos gene expression, caused increases in jun-B and fos-B that preceded the decrease in albumin mRNA levels at 24 hours. These observations are consistent with our hypothesis that jun-B and fos-B induction may participate in downregulation of albumin synthesis as well as other hepatic responses to TGF-beta.


Strategies in the surgical treatment of malignant ventricular arrhythmias. An 8-year experience. Introduction of the automatic implantable cardioverter defibrillator (AICD) has dramatically affected the surgical treatment of malignant ventricular tachyarrhythmias. The authors continue to perform electrophysiologically directed subendocardial resection (SER) of left ventricular (LV) scars in selected patients, and we revascularize (CABG) those patients undergoing AICD implantation who have significant myocardial ischemia. In an attempt to define the optimal role of each procedure, this report analyzes our 8-year experience with 348 consecutive patients treated surgically for these arrhythmias (SER since 1983 and AICD since 1986). All patients undergoing SER had organized ventricular tachycardia (VT) as a result of myocardial infarction, and most had LV aneurysms; of those undergoing AICD or AICD/CABG, 60% had VT, 15% had ventricular fibrillation, and 25% had both or were noninducible. The thirty-day mortality rate was 1.5% (3/197) for AICD, 5.4% (5/93) for AICD/CABG, and 8.6% (5/58) for SER; these mortality figures are not significant different. Late deaths in all groups were predominantly due to congestive heart failure, and actuarial survival as well as freedom from sudden death was similar between the groups at 4 years. Recurrent VT occurred in 167 of 282 (59%) of long-term survivors of AICD or AICD/CABG during follow-up and in nine of 53 (17%) of those with SER. Forty-eight per cent of survivors of AICD or AICD/CABG required antiarrhythmic medications, whereas only 11% of those with SER required antiarrhythmics. Long-term survival in each group is much higher than that reported for comparable patients with severe LV dysfunction treated medically. In those patients with organized VT and LV aneurysm who are judged able to survive the procedure, SER offers a high likelihood of cure rather than simple prevention of sudden death.


Surgical management of dysrhythmias in infants and small children. Surgery for cardiac dysrhythmias is infrequently reported in infants and children as compared with adults. This report reviews 55 infants and small children (age, less than or equal to 5 years) operated on during the interval July 1, 1984 to December 31, 1991 for Wolff-Parkinson-White Syndrome (41), atrioventricular node reentry (two), atrial automatic tachycardia (two), and ventricular tachycardia (nine). Ages ranged from 3 weeks to 71 (mean, 29) months. Associated congenital heart defects were present in five (10%). Indications for surgery included failure of medical therapy, life-threatening dysrhythmias, and more recently, failure of catheter ablation. There were no hospital or late deaths. One patient sustained perioperative central nervous system injury. Surgery was successful in 52 of 55 (94.5%) (Wolff-Parkinson-White, 38/41 (93%); atrioventricular node reentry, 2/2 (100%); atrial automatic tachycardia, 3/3 (100%); ventricular tachycardia, 9/9 (100%). Ventricular function returned to normal in all 12 patients in whom it was abnormal before operation. Thus, surgical ablation is highly successful in the management of various forms of refractory or life-threatening dysrhythmias in infants and small children. Catheter ablation techniques require significant fluoroscopic time, are more difficult in infants, and as yet do not have adequate long-term follow-up. Accordingly, surgery may continue to play a role in this particular group of patients.


Smooth muscle cell elastase, atherosclerosis, and abdominal aortic aneurysms. Smooth muscle cells (SMC) were obtained by outgrowth of human aortic explants from abdominal aortic aneurysm (AAA) patients, aortic occlusive disease (AOD) patients, and transplant donors (controls). Specimens were incubated with medium alone or medium with either elastin-derived peptides (EDP, 5 micrograms/mL) or low-density lipoproteins (LDL, 5 micrograms/mL). Elastase activity (ng/mg total protein) was assayed from 4-week-old cultures. Control aortas obtained from patients significantly younger secrete an increased amount of elastase at baseline compared with AOD and AAA patients (p less than 0.05). Elastin-derived peptides caused a significant increase in elastase secretion in all groups. The increase in elastase secretion in response to EDP in AAA patients was significantly higher compared with AOD or control. Low-density lipoprotein had no effect on SMC elastase secretion. These data suggest that (1) aortic SMCs secrete elastase in response to EDP, (2) SMC elastase is age dependent, and (3) AAA SMC secrete an abnormally high amount of elastase compared with AOD and control aortas in response to EDP. Like the neutrophil, the SMC is highly responsive to the degradation products of elastin and in AAA patients secrete significantly increased amounts of elastase in response to the breakdown products of atherosclerosis.


Long-term surgical results in sudden death syndrome associated with cardiac dysfunction after myocardial infarction. To evaluate the surgical results in patients with inducible ventricular tachyarrhythmias due to coronary disease and left ventricular dysfunction, the authors reviewed their experience in 170 patients who had survived one or more cardiac arrests after myocardial infarction and were unresponsive to drug therapy based on electrophysiologic studies (EPS). There were nine operative deaths (5%). Based on intraoperative EPS, surgical remodeling of left ventricular dysfunction (aneurysm resection, infarct debulking, and septal reinforcement) with map-guided cryoablation and coronary artery bypass graft was performed in 34 patients (group A), and left ventricular remodeling and coronary artery bypass graft without guided endocardial resection was performed in 25 patients (group B). Forty-three patients (group C) had coronary artery bypass graft with implantation of an automatic implantable cardioverter defibrillator (AICD). Group D (68 patients) received AICD only. After operation, based on EPS results, four patients in group A (12%) and three patients in Group B (15%) required AICD implantation. Overall survival at 6 years was 65%, 48%, 85%, and 58% in patient groups A, B, C, and D, respectively (p = not significant). During follow-up in group A patients, none died suddenly and none needed AICD. In group B, two patients required AICD 3 and 5 years later, and five patients died suddenly. The incidence of sudden death was 2.3%/patient/year and 3.5%/patient/year after AICD implantation (groups C and D). At 6 years, cardiac-event-free survival was 80% and 70% for groups A and B and 38% and 24% for groups C and D, respectively (p less than 0.001). Patients receiving map-guided ablative procedures had significantly improved cardiac-event-free survival rates.


Biliary strictures complicating liver transplantation. Incidence, pathogenesis, management, and outcome. Six hundred sixty-six patients received 792 liver transplants between February 1, 1984 and September 30, 1991. Biliary reconstruction was by choledochocholedochostomy (CDCD) with T-tube (n = 509) or Roux-en-Y choledochojejunostomy (CDJ) (n = 283). Twenty-five patients (4%) developed biliary strictures. Anastomotic strictures were more common after CDJ (n = 10, 3.5%) than for CDCD (n = 3, 0.6%). Intrahepatic strictures developed in 12 patients. Six patients had occult hepatic artery thrombosis (HAT). The other six patients received grafts in which cold ischemia time exceeded 12 hours. Anastomotic strictures were successfully managed by percutaneous dilation (PD) in five patients (n = 10), operation in three (n = 6), with retransplantation required in two patients. Intrahepatic strictures were managed by PD in seven, retransplantation in one, and expectantly in four patients. Of 25 patients, 19 (76%) are alive with good graft function. In three of six deaths, the biliary stricture was a significant factor to the development of sepsis and allograft failure. The authors conclude that (1) anastomotic strictures are rare after LT; (2) the development of biliary strictures may signify occult HAT; (3) PD is effective for most strictures; and (4) extended cold graft ischemia (less than 12 hours) may be injurious to the biliary epithelium, resulting in intrahepatic stricture formation.


Pulmonary autograft replacement in children. The ideal solution? Fifty-one children, aged 1.8 to 21 years (mean, 11.4) with aortic valve replacement using a pulmonary autograft are reviewed. Twenty-nine were intra-aortic implants and 22 were root replacements. There was one operative death, no late deaths, and two have required reoperation. Actuarial freedom from reoperation was 93% +/- 5.5 at 5.6 years. Freedom from progression of aortic insufficiency (AI) was 81% +/- 9 at 5.6 years in the intra-aortic implants and 86% +/- 10 in the root replacement. Enlargement of the pulmonary autograft was seen echocardiographically in both groups. This enlargement was consistent with somatic growth and not associated with progression of AI. Ten of 19 patients with aortic stenosis had an LV mass index suggestive of LV hypertrophy before operation. At 1 year, 18 of 25 had a normal LV mass index. Thirteen of 16 patients with AI had preoperative abnormal LV mass index. All but four returned to normal by 1 year. Low operative risk, excellent function, resolution of abnormal LV hemodynamics, and enlargement consistent with somatic growth suggest that the pulmonary autograft is the ideal replacement for the malfunctioning aortic valve.


Adherent neutrophils mediate permeability after atelectasis. Re-expansion of atelectatic lung is associated with increased permeability. This study tests whether neutrophils mediate this event. Right middle lobar atelectasis was induced in anesthesized rabbits (n = 18) by intraluminal obstruction of the bronchus after a 20-minute ventilation with 100% O2. After 1 hour of bronchial obstruction and 20 minutes after lobar re-expansion, leukopenia was noted, 2870 +/- 210 white blood cells (WBC)/mm3, relative to control animals treated with a noninflated balloon catheter, 6500 +/- 410 WBC/mm3 (p less than 0.05). Three hours after re-expansion, neutrophils were sequestered in the previously atelectatic region 78 +/- 7 polymorphonuclear leukocytes (PMN)/10 high-power field (HPF), as well as in nonatelectatic areas, 40 +/- 3 PMN/10 HPF, higher than control values of 26 +/- 3 PMN/10 HPF (p less than 0.05). In the atelectatic region, neutrophil sequestration was associated with increased protein concentration in lobar bronchoalveolar lavage (BAL) of 1370 +/- 100 micrograms/mL, higher than control values of 270 +/- 20 micrograms/mL (p less than 0.05). Reexpansion also induced increases in lung wet-to-dry weight ratio (W/d) of 6.2 +/- 0.2, higher than control values of 4.3 +/- 0.1 (p less than 0.05). Rendering rabbits neutropenic (n = 18) (0 to 4 PMN/mm3) limited the atelectasis-induced protein accumulations in BAL (520 +/- 60 micrograms/mL) and increase in lung W/d (5.2 +/- 0.1) (both p less than 0.05). Intravenous (I.V.; treatment of another group (n = 18) with an anti-CD 18 monoclonal antibody (R 15.7, 1 mg/kg) before balloon deflation prevented leukopenia (6550 +/- 560 WBC/mm3), minimized neutrophil sequestration (36 +/- 2 PMN/10 HPF), and attenuated protein leak (710 +/- 95 micrograms/mL) and the increased lung W/d (5.6 +/- 0.1) (all p less than 0.05). A final atelectatic group (n = 9) was treated I.V. with the anti-intercellular adhesion molecule-1 monoclonal antibody (RR 1/1, 1 mg/kg), which also prevented leukopenia and showed similar protection of microvascular barrier function. These data indicate that adherent neutrophils in large part mediate lung permeability and edema after atelectasis and re-expansion. Adhesion receptors of both neutrophils and endothelial cells regulate this event.


Muscle protein breakdown during endotoxemia in rats and after treatment with interleukin-1 receptor antagonist (IL-1ra). The purpose of this study was to examine the effect of endotoxemia on muscle protein degradation and to test the hypothesis that muscle proteolysis during endotoxemia is regulated by interleukin-1 (IL-1). Both total and myofibrillar protein breakdown rates in incubated extensor digitorum longus muscles were increased after the subcutaneous injection of 0.1 or 1.0 mg/kg endotoxin in rats. The endotoxin-induced increase in muscle protein breakdown was blunted by IL-1 receptor antagonist, administered intraperitoneally at a total dose of 45 or 105 mg/kg. Results suggest that endotoxemia in rats gives rise to sepsislike changes in muscle protein breakdown. Increased muscle protein breakdown during endotoxemia may be regulated, at least in part, by IL-1.


Women in the POSCH trial. Effects of aggressive cholesterol modification in women with coronary heart disease. The POSCH Group. Program on the Surgical Control of the Hyperlipidemias. The Program on the Surgical Control of the Hyperlipidemias (POSCH) provided the clearest and the most convincing evidence supporting the beneficial effects of cholesterol lowering in hypercholesterolemic survivors of a myocardial infarction. In POSCH, 78 of the 838 patients (9.3%) were women, with 32 randomized to the diet-control group and 46 to the diet plus partial ileal bypass surgery-intervention group. At 5 years, the mean per cent change from baseline was -23.9% for total plasma cholesterol (p < 0.0001), -36.1% for low-density lipoprotein cholesterol (p < 0.0001), and +8.5% for high-density lipoprotein cholesterol (p = not significant). Because of the small number of women, no statistically significant changes in clinical event rates were observed between the control and the surgery groups. A comparison of 162 coronary arteriography film pairs in the POSCH women, between baseline and 3, 5, 7, and 10 years, consistently showed less disease progression in the surgery group (p = 0.013 for combined assessments of the baseline to the longest follow-up film). Because the lipid and coronary arteriography findings in the POSCH women paralleled these findings in the total POSCH population and in the POSCH men, and because the arteriography changes in POSCH have previously been demonstrated to be statistically significant surrogate end points for certain clinical events and predictors of overall and atherosclerotic coronary heart disease mortality rates, we conclude that the lipid modification achieved in the POSCH women by partial ileal bypass reduced their atherosclerosis progression. The POSCH findings in women support the aggressive treatment of hyperlipidemia in the general management of atherosclerosis in women.


The safety and effect of topically applied recombinant basic fibroblast growth factor on the healing of chronic pressure sores. The first randomized, blinded, placebo-controlled human trials of recombinant basic fibroblast growth factor (bFGF) for pressure sore treatment were performed. Three different concentrations of bFGF in five dosing schedules were tested for safety using hematology, serum chemistries, urinalysis, absorption, antibody formation, and signs of toxicity. Efficacy was evaluated by wound volumes, histology, and photography. No toxicity, significant serum absorption, or antibody formation occurred. In six of eight subgroups, there was a trend toward efficacy with bFGF treatment. When all subgroups were combined, comparison of the slopes of the regression curves of volume decrease over initial pressure sore volume demonstrated a greater healing effect for the bFGF-treated patients (p < 0.05). Histologically, bFGF-treated wound sections demonstrated increased fibroblasts and capillaries. More patients treated with bFGF achieved > 70% wound closure (p < 0.05). Blinded observers were able to distinguish differences in visual wound improvement between bFGF and placebo groups. These data suggest that bFGF may be effective in the treatment of chronic wounds.


Intrathymic injection of donor alloantigens induces donor-specific vascularized allograft tolerance without immunosuppression. The induction of donor-specific tolerance could prevent the side effects of immunosuppression while improving allograft survival. Male adult Buffalo (RT1b) rats underwent an intrathymic (IT), portal venous (PV), intrasplenic (IS), or subcutaneous (SQ) injection of 25 x 10(6) major histocompatibility complex (MHC) mismatched Lewis (RT1(1)), UV-B-irradiated Lewis (RT1(1)), ACI (RT1a), or syngeneic Buffalo (RT1b) splenocytes. At the completion of the donor alloantigen injection, 1 mL rabbit anti-rat lymphocyte serum (ALS) was administered intraperitoneally to the Buffalo recipients, and 21 days later a heterotopic Lewis or ACI heart was transplanted. Intrathymic injection of donor alloantigen induced a donor-specific tolerance that allowed the cardiac allograft to survive indefinitely (mean survival time [MST] > 140.7 days) in 84% of the recipients without further immunosuppression, whereas groups receiving antigen injections at other sites (PV, IS, and SQ) plus ALS rejected cardiac allografts in normal fashion (MST approximately 8.0 days). Buffalo recipient rats with long-term surviving Lewis cardiac allografts after Lewis IT injection and ALS subsequently rejected a heterotopic third-party ACI cardiac allograft in normal fashion (MST approximately 7 days), whereas a second Lewis cardiac allograft was not rejected (MST > 116 days). Microchimerism is unlikely because Lewis allograft survival was also prolonged (MST > 38.7 days) in rats receiving UV-B-irradiated splenocytes IT, which cannot proliferate. Survival of Lewis renal allografts was also prolonged, but not indefinitely, in Buffalo recipients possessing a long-term surviving Lewis cardiac allograft (MST approximately 17.6 days versus 7 days for control). This model emphasizes the potential role of exposure of immature thymocytes to foreign donor alloantigens during maturation in the thymic environment for the development of unresponsiveness to an MHC-mismatched donor-specific vascularized allograft.


Intestinal radioprotection by two new agents applied topically. The purpose of this study was to test two novel antioxidant drugs, each capable of inhibiting membrane peroxidation and of free radical scavenging, as topical radioprotectants for the intestine. A loop of rat midintestine was exteriorized and radiated while the remainder of the animal was protected in a lead box. The intestine was first compartmentalized and each segment filled with a test solution. Radiated segments of intestine were compared, drug filled with vehicle filled, and both with normal unradiated intestine. The animals were killed 5 days after 1100 cGy radiation to the exteriorized loop. Crypt numbers and mucosal height were used as the measures of injury protection. On the basis of crypt numbers, the 21-amino steroid (U-74500A) gave approximately 40% and the vitamin E-like compound (U-78518F) gave 60% reduction in crypt loss. The authors conclude that lumenal antioxidant drugs can provide partial protection of the intestinal mucosa from acute radiation damage and that these two specific agents are effective and potentially useful.


Surgical treatment of tumors of the distal rectum with sphincter preservation. One hundred one patients with villous adenoma or invasive carcinoma of the distal rectum treated with local excision or coloanal anastomosis were studied. Twenty-three (45%) of the 51 patients with villous adenomas had transanal excision, another 23 (45%) had a posterior proctotomy, and five (10%) had a coloanal anastomosis. Only two patients with a villous adenoma developed a recurrence requiring repeat local excision. Fifteen (30%) of the 50 patients with invasive cancer were treated by transanal excision. All had tumors confined to the submucosa or superficial muscularis. Eighteen (85%) of 21 patients having posterior proctotomy also had tumors with similar depth of invasion. Six (43%) of the 14 patients having coloanal anastomosis had Dukes' B tumors, six (43%) were Dukes' C, and another two (14%) underwent palliative resection. The overall actuarial 5-year survival was 77%. Only four patients treated by transanal excision or posterior proctotomy died of metastatic disease. In the coloanal group, two of 12 patients undergoing curative resection died of recurrent cancer, and another has a pelvic recurrence. Villous adenomas of the distal rectum and selected carcinomas may be treated with local excision and coloanal anastomosis with preservation of sphincter function with good results.