Chemoradiotherapy in locally advanced bladder carcinoma.

Bladder carcinoma represents the fifth leading cause of cancer in the United States. For patients with muscle-invasive tumors, radical cystectomy has been the treatment of choice, yet over 50% of such treated patients are destined to develop recurrent disease. In order to minimize morbidity in patients with invasive disease, bladder-sparing techniques using radiotherapy alone, or with chemotherapy, have been investigated. While it is clear that durable complete remission can be achieved in some patients, the results to date require additional follow-up to determine the optimal cohort of patients destined to benefit from this approach. It is hoped that ongoing prospective trials will delineate this population.


Combined radiotherapy and chemotherapy in the treatment of gastrointestinal malignancies.

There has long been an interest in the use of combination chemotherapy/radiotherapy in the treatment of gastrointestinal tumors. Almost all such regimens combined 5-fluorouracil (5-FU) with radiotherapy. Work has been done in gastric cancer, pancreatic cancer, and colon and rectal cancer, all of which demonstrate an advantage in certain clinical situations for combined-modality therapy. In locally advanced pancreatic cancer, radiotherapy/5-FU has been shown to improve survival compared with radiotherapy alone, while in resectable carcinoma of the pancreas, the combination has been demonstrated to improve long-term survival compared with surgery alone. In patients with gastric cancer the data are more limited, but indications are that combined-modality therapy may benefit certain subsets of patients. Little information exists in colon cancer, but patterns of failure suggest a potential role for adjuvant radiotherapy/5-FU. Studies are being designed to test the hypothesis. In rectal cancer, a significant amount of data exists to support the value of radiotherapy/5-FU-based chemotherapy as an adjuvant in patients with stages B2 and C tumors. At present, studies are being run or analyzed to define whether modulation of 5-FU with leucovorin or levamisole, or whether the use of continuous infusion 5-FU, will improve the therapeutic efficacy of the adjuvant therapy.


Therapeutic use of immunotoxins.

Much progress has been made in the therapeutic use of immunotoxins since the first clinical trials, especially in the prevention and treatment of AGVHD. This is also further discussed in this symposium by Champlin. Research in immunotoxin use has gone beyond cancer and into the treatment of immunologic disorders, such as rheumatoid arthritis and HIV infection. Before further advances can take place several problems must be overcome, including the rapid clearance of immunotoxin by the liver, the generation of anti-immunotoxin antibodies, and poor penetration by the immunotoxin in solid tumors. Other obstacles to the wide use of immunotoxins are the heterogeneity of tumor cells, the shedding of tumor antigens into the circulation, and the inability to identify neoplastic renewal cell specific antigens that are not cross-reactive with normal tissues. Despite these obstacles, the early success of immunotoxins, especially in hematologic malignancies, reinforces the feasibility of designing rational targeting reagents in cancer therapy.


Role of intravenous immunoglobulin G in autoimmune hematologic disorders.

The data presented in this review established IVIG therapy as an important treatment modality in the autoantibody-mediated cytopenias and coagulation disorders of both children and adults. The immediate response to therapy is thought to be related to nonspecific Fc-receptor blockade of mononuclear phagocytes in the reticuloendothelial system (autoimmune cytopenias), or to idiotypic antibody interaction with pathologic autoantibodies (in acquired coagulation disorders). Although less frequent, long-term responses to IVIG therapy are reported. Such responses must involve an immunomodulating effect of IgG that influences T- and B-cell function, with inhibition of pathologic autoantibody formation. It is possible that idiotypic antibody interactions play a part in long-term responses. The experience with IVIG therapy in the decade following Imbach's important observations reported in 1981 has provided a sound data base regarding the use of this important therapy in patients with autoimmune hematologic disorders. The challenge of the next decade should be to further investigate mechanisms of action of this important therapy and to conduct carefully controlled studies to answer specific clinical questions. Examples of such questions include the following: (1) Can IVIG therapy, administered early in the course of illness in selected children with acute ITP, decrease the incidence of chronic ITP?; (2) Is maintenance, high-dose IVIG therapy a cost-effective method for the management of patients with chronic ITP refractory to corticosteroid therapy and splenectomy?; and (3) Can IVIG therapy administered to selected pregnant women with ITP significantly reduce the incidence of serious thrombocytopenia in their offspring? In conducting these studies, consideration should be given to the type of IVIG preparation used and to the treatment protocol implemented. It is evident that responses to unmodified IgG preparations (with the Fc-receptor part of the molecule left largely intact) are superior to preparations that have been modified during preparation. Responses are also likely to be dose-related. The data reported for IVIG therapy in patients with acquired factor VIII deficiency suggests that the idiotypic antibody content of IgG preparations is also of importance; if so, preparations selected from specific donor pools (for example, multiparous women) known to contain higher levels of circulating autoantibodies (than those from primiparous women or untransfused males) may provide a degree of benefit not seen with standard IVIG preparations. It is therefore important that clinicians and laboratory specialists work closely together in the design and conduct of future clinical trials initiated to answer those important clinical questions raised by the first decade of observations with IVIG therapy for autoimmune hematologic disorders.


Alloimmunization to platelet antigens.

Alloantibodies to platelet-specific antigens can cause significant thrombocytopenia and bleeding in NATP and PTP. IVIG plays an important role in the therapeutic regimen of both of these disorders. Alloantibodies in the multiply transfused patient bind to HLA class I and platelet-specific antigens. IVIG has not improved response to random-donor platelets in refractory patients, but there may be a role for IVIG in critically ill and bleeding patients, in combination with HLA-matched platelets.


Psychosocial problems in primary care: some results from the Dutch National Study of Morbidity and Interventions in General Practice.

According to standardized screening instruments, mental distress is a common phenomenon among many patients who visit their general practitioner. However, a number of patients who seem to be in need of mental help do not put forward such a demand for help, whereas other patients who express psychosocial problems to their GP are not considered to be in need, according to a standardized measure. In this paper, a distinction has been made between the objectified needs of the patient as expressed by a standardized assessment, and the demands of the patient, expressed by the Reason for Encounter, stated during their visit at the GP. Results of a follow-up study of two cohorts of patients have been presented: one cohort presented during a 3 month period at least one articulated demand for psychosocial help, a second cohort presented at least one somatic complaint, considered by the GP as being psychological by character, without presenting any psychosocial complaint in that period. Objective needs for mental help of patients in both cohorts were assessed by means of the General Health Questionnaire. During one year all consultations of these two cohorts were registered. The following questions have been put forward: what demands for help have been put forward by the patients, what treatment have these patients got, and what has been the course of the problems during one year of patients with different needs and demands. From the results the following conclusions may be drawn: many patients with a probable mental illness (according to their objective need) present only physical symptoms.(ABSTRACT TRUNCATED AT 250 WORDS)


Policy directions in urban health in developing countries--the slum improvement approach.

The urban development, or housing, sector has a longer experience of addressing the problems of the urban poor in developing countries than the health sector. In recent years the policy of 'slum improvement', which involves both sectors, has attracted the support of international donors. This article documents the development of the slum improvement approach and addresses key issues of the approach which have implications for health planning: covering the poorest dwellers; relocation; land tenure; gentrification; debt burdens and the impact on women. Questions about the approach which still need answering are defined and a summary of the constraints in slum improvement and potential solutions is presented.


Sexually transmitted disease, ethnomedicine and health policy in Africa.

Compared with both industrialized countries and other less developed parts of the world, most of sub-Saharan Africa suffers inordinately from sexually transmitted diseases (STDs). It has high prevalence rates of traditional STDs, such as gonorrhea and syphilis, and if accurate seroprevalence surveys were to be done, it would probably prove to have the highest HIV seropositive incidence in the world. Unlike the pattern in the West, AIDS is primarily a heterosexually transmitted disease in Africa. This appears to be largely because of the prevalence of other untreated or improperly treated STDs. Therefore to lower the incidence of STDs would be to curtail the spread of HIV infection. The problem becomes how exactly to accomplish this. Most STD cases are never even presented at biomedical health facilities; they are presented to traditional healers. Both healers and their patients seem to believe that traditional STD cures are more effective than 'modern' cures, although the former are probably biomedically ineffective. While there is scant ethnomedical literature on STDs in Africa, the present paper presents Swaziland findings and related evidence from other African societies that the ultimate cause of several common STDs is believed to be the violation of norms governing sexual behavior, requiring traditional rather than biomedical treatment. Traditional healers therefore need to be a central part of any scheme to lower the incidence of STDs.


Malaria: ethnomedical perceptions and practice in an Adangbe farming community and implications for control.

Malaria is a parasitic disease about which there is much bio-medical knowledge on causation, prevention, treatment and control. Attempts at eradication, as well as control in the past has been mainly a technical and bio-medical endeavour. With the policy shift from world wide eradication of malaria to control as part of primary health care, there is increasing interest in studying all possible determinants of the problem at local as well as regional levels as part of the search for an effective intervention. This paper presents the results of a study into community perceptions and practice relating to causation, treatment and prevention of malaria in a rural Adangbe farming community in Southern Ghana. Malaria is common in this community. Crude parasite rates among adolescent girls (10-19 years old) in the community were 49% towards the end of the major rainy season, and 47% in the early dry season. The symptoms and signs of the disease are readily described by lay people as well as traditional healers. Diagnosis and treatment of uncomplicated episodes of malaria at home, according to ethnomedical perceptions, is the predominant behaviour in this community. Very few cases of uncomplicated malaria are sent to health facilities. Ethnomedical perceptions of malaria causation and treatment on which this self care is based, are different from conventional biomedical ones. Malaria is perceived as an environmentally related disease caused by excessive contact with external heat which upsets the blood equilibrium. Many community members do not connect it with the mosquito in theory or practice. Implications for approaches to control are discussed.


Quality of Life in patients with resected oesophageal cancer.

Quality of Life (QL) is hard to assess and seldom measured in patients having carcinomas with an unfavourable prognosis. Oesophageal cancer is one of the malignancies with a low 5-year survival rate. Dysphagia (problems in swallowing food) is considered to be the most important indicator of QL in patients with oesophageal carcinoma. Moreover, the psycho-social aspects and subjective QL in cancer have recently gained importance. The present study investigated QL in a 132 patients with oesophageal cancer. Eighty-three of them had a surgical operation (removal of part of the oesophagus and part of the stomach, followed by a reconstruction of the digestive tract). Sixty-seven patients filled in questionnaires before and after the operation. Complete sets of data were obtained from 62 patients. Time interval between operation and postoperative assessment varied from 3 to 7 months. Indicators of QL were: Psychological Distress, Physical Symptoms, Global Evaluations, Activity Level, Swallowing Problems and Food Intake. Swallowing Problems showed moderate correlations with the other QL indicators. Physical Symptoms increased, whereas the Activity Level, Psychological Distress, and Swallowing Problems decreased; Global Evaluations remained unaltered.


Syphilis, sex and crack cocaine: images of risk and morality.

A new epidemic of syphilis in the Portland, Oregon metropolitan region mirrors a national trend in the United States. The epidemic is centered in urban areas, is associated with heterosexual transmission, and disproportionately affects people of color, especially African-Americans. The epidemic has been linked to sexual activity among users of crack cocaine, and particularly to the practice of trading sex and crack. Here, we report an analysis of in-depth interviews of 40 respondents, of whom 31 have used crack cocaine, 12 have experience as professional sex workers (prostitutes), and 12 are confirmed recent syphilis cases or their sexual contacts. These respondents confirm that sexual activity involving multiple anonymous partners often takes place within the context of crack cocaine use. They also describe sexual activity among more casual users of the drug. But respondents present themselves as having maintained an adherence to common American values regarding cleanliness, mortality, and sexual behavior. They speak of choosing sex partners according to whether a prospective partner 'looks clean.' This image of cleanliness goes beyond simple bodily hygiene, and into the realm of judgement about moral character. A person is more likely to be judged clean if he or she is known to come from a nice family, has a pleasant demeanor, or appears concerned about self-control. Such people are seen as fundamentally decent, and therefore less likely to have syphilis, a disease associated with deterioration, tearing down, dirtiness and disordering. Thus, respondents use conceptions of cleanliness and morality in constructing definitions of high- and low-risk sexual behavior, as they negotiate a life that endangers their sense of moral control. In doing this, they invoke beliefs and values central to the dominant culture surrounding them. This points to the limits of defining crack cocaine users, and other communities of drug users, as being culturally different from the rest of us.


Economic appraisal of asthma and COPD care: a literature review 1980-1991.

Despite the considerable burden and costs of illness and despite the increasing need to set priorities on the basis of efficiency considerations, only 20 economic appraisals of asthma and COPD care have been published during the past 11 years. This paper provides a detailed summary of the cost-effectiveness 'evidence' given by these studies and a discussion of relevant methodological issues. The studies comparing programme costs of delivery methods for oxygen and for aerosol bronchodilator drugs, provide the most straightforward evidence in favour of the concentrator and the metered dose inhaler respectively. There also seems to be evidence in favour of hospital-based home care programmes as compared to community-based home care programs. Health education, especially directed at asthmatic children seems to reduce health care costs and improve attitude, compliance behaviour and self-management skills. Information on the cost-effectiveness of pharmacotherapy and diagnostic technologies, both important interventions in asthma and COPD, was found to be totally lacking.


Kidney procurement policies in the Eurotransplant region. 'Opting in' versus 'opting out'.

A shortage of kidneys has been part of kidney transplantation ever since it evolved from its experimental stage and became a therapeutic possibility. However, at present this shortage is more acute than ever before. Post mortem kidney procurement policies can be distinguished into 'opting in' and 'opting out' systems. In the five countries cooperating in Eurotransplant, systems of both kind have been implemented. In this paper the relation between these procurement policies and kidney availability in the Eurotransplant region is examined. The opting out system turns out to be more favourable to kidney procurement than the opting in system. The approach of the next of kin with the donation question happens to be an important barrier for kidney procurement in the opting in system, but fails to appear under opting out. In the epilogue some remarks are made on the possibilities of introduction of the opting out system in countries now applying opting in.


A classification of psychological distress for use in primary care settings.

This paper contrasts three ways of conceptualizing emotional distress in general medical settings: high scorers on screening tests, 'cases' according to the doctor seeing them, and standardized research diagnoses. It is shown that distress as measured by screening test is very much more prevalent than research diagnosis, and yet doctors working in general medical settings need to be able to conceptualize disorders using a classification that is helpful for them. The proposed classification is based upon the patient's need for intervention, and it distinguishes the few who need to be thought of as having a formal mental disorder from the many who do not. It takes account of what is known about 'labelling' and compliance, and it is linked to the skills needed by primary care workers. The largest group consists of those whose emotional distress needs recognition and discussion; the next group also needs social interventions; while the final group benefits from recognition of a mental disorder which necessitates a medical or psychological treatment.


Mortality from selected cancers in NSW and Sydney, Australia.

This study utilizes unit list mortality data for New South Wales, Australia in differential mortality analysis, at state and local levels, and examines geographic patterns of stomach, colo-rectum, respiratory system, female breast cancer and total cancer mortality in Sydney. Associations between manual occupations, low socioeconomic status and male stomach and respiratory cancer mortality were found, as were higher mortality from stomach and respiratory cancer among European-born immigrants in manual occupations. However, unexpected associations were also found between high mortality from stomach and respiratory cancers and managerial occupations. There were also more acute associations between colo-rectum and female breast cancer and higher status areas. Further, mortality variations between specific occupational groups occurred when martial status was controlled for, and the strongest variations were between married and never married males where the social isolation risk factors were presumed to be operative. The highest mortality at the local level in Sydney occurred where more than one at risk population resided and where other influences may have been operative.


Professional reimbursement and management of time in general practice. An international comparison.

A hypothetical model was proposed for explaining the relationship between general practitioners' system of payment and the amount of time spent in patient and non-patient work. It was hypothesized that GPs reactions to higher workload vary according to the payment system. In this paper we compare two health care systems which have both mixed systems of payment of GPs. In England and Wales up until April 1990 GPs are partly paid by capitation (approx 45% of their income), partly by allowance (38% of their income) and for a much smaller part fee for service (18% of their income). In the Netherlands GPs are paid by capitation for the publicly insured patients (63% of the average practice list) and fee for service for the privately insured patients. We expect (among other things) a stronger, positive relationship between list size and hours worked in the Netherlands and a comparably strong, negative relationship between list size and booking intervals in the Netherlands and in England and Wales. Drawing on data collected from national surveys of GP workload in the Netherlands and England and Wales these propositions were examined. The results of this comparative analysis showed some support for the propositions in that the relation between list size and number of hours worked in patient related activities is stronger in the Dutch setting than in England and Wales, and about the same strength for the relationship between list size and booking intervals.


Integrating conflicting professional roles: physician participation in randomized clinical trials.

The traditional identification of physicians as either clinician or researcher is challenged by the emergence of randomized clinical trials (RCTs) where research and clinical care are performed simultaneously. A mail survey using a self-administered questionnaire, the Physician Orientation Profile, was conducted of 101 physicians from the Collaborative Ocular Melanoma Study (COMS), a set of trials which compares surgical removal of the eye with radiation in the treatment of medium sized eye cancers. A 95% response rate was obtained; follow-up telephone interviews were conducted with 87% of respondents. Key findings suggest that RCTs challenge traditional definitions of physician's 'core task,' because they participate in a social process that requires them to integrate the formerly disparate and sometimes competing roles of researcher and clinician. Three implications of this integration are discussed: amending the expert reward system, altering customary clinical practice and redefining reference groups for professional interaction.


[Total prosthesis of the hip joint for traumatic indications (VUTSCH data from 1985-1990)].

The authors analyze all total endoprostheses which were performed at their department in 1985-1990 for traumatic indications--an injury or its immediate sequelae: 6 times an implantation was made because of fracture, 11 times because of failure of primary synthesis or serious aseptic necrosis of the head after synthesis. There were no prostheses on account of late deforming arthritis which developed on a posttraumatic background. Seventeen total endoprostheses made on account of traumatic indication account for 7.4% of all total endoprostheses during the period of investigation. One patient died from pulmonary embolism after the operation, although heparin prevention was used and one patient developed a minor complication. All eight patients who were checked on average after 22.4 months following implantation had excellent or good results. The authors reached the conclusion that total endoprostheses should be indicated more frequently to the benefit of younger casualties and that the total numbers of total endoprostheses on account of traumatic indications are low. Therefore it is necessary to concentrate alloplasties mainly on orthopaedic departments which have experience also with other indications. Certain types of fractures of the neck and head of the femur or acetabulum cannot treated nowadays as effectively by any other technique.


[Experience with non-surgical treatment of splenic injuries].

Since 1980 in the department of paediatric surgery in Prague-Krc injury of the spleen is no longer an absolute indication for laparotomy and splenectomy. During the period from 1980-1990 46 children were admitted with an injured spleen. Of these 35 (76%) were treated conservatively, 11 children were operated. The number of conservatively treated patients increased in the course of time--during the initial period before 1985 65% children were treated conservatively, from 1986 to 1990 already 90% children. Only 16% children with an injured spleen treated conservatively needed a blood transfusion (on average 18.1 ml/kg body weight). This experience indicates that the great majority of children with an injured spleen can be treated by non-surgical methods. It is necessary to respect certain criteria which are given in the paper. Laparotomy is necessary in children with unstable vital functions, associated intraabdominal injuries and those to whom more than 30 ml blood per kg body weight must be administered.


[Arterial injuries of the upper extremities].

At the Department of Surgery in Pilsen in 1982-1991 a total of 26 patients with upper extremity vascular injuries was treated. Brachial artery was injured most commonly (50%). The direct trauma was responsible for 88.5% injuries, indirect injury was recorded in 11.5% cases only. The incidence of concomitant injuries of the vein, nerve or bone was 73.1%. Approximately one third of arterial injuries was caused by criminal offences. The vascular reconstruction was performed in all 26 patients. The overall patency rate was 84.6%, the amputation rate was 3.8%. One patient with polytrauma died of sepsis (3.8%). The authors give a comprehensive review of the causes, diagnosis and treatment of vascular injuries of the upper extremities.


[The cervico-capital endoprosthesis in traumatology. Experience of the Traumatology and Special Surgery Research Institute 1985-1990].

The authors submit an analysis of a group of 143 patients to whom in 1985-1990 in the Traumatological Research Institute in Brno a cervicocapital endoprosthesis was implanted. Indication for implantation was in all instances a fracture of the neck of the femur, most frequently a subcapital fracture--a total of 92. Women predominated 5:1. The mean age was 75 years, the range 37-93 years. In 119 patients the endoprosthesis was implanted on account of a new injury, in the remaining 24 on account of the sequelae of an injury. In 32 patients 1-4 operations preceded. The most frequent cause was a fall in the home. Fifteen patients were operated on the day of the injury and 80 were operated within five days after the injury. In the group 60 complications were recorded, 1-4 complications in 46 patients (32% of the group). The causes of complications are discussed. During the investigation 46 patients died (32% of the group), incl. half during the first hospitalization on account of the investigated injury. Only 27 patients of the group could be followed up, results are presented (excellent and good in 20 patients) and the reasons are discussed why patients cannot be followed up. Finally the authors conclude that in future it will be necessary to indicate endoprostheses as primary treatment more frequently, although secondary operations have similar results. The operation should be made as soon as the patient's condition permits it; the urgency is not acute as in syntheses; it should permit early mobilization of the patient. The unsatisfactory percentage of complications must be reduced by a complex of measures starting with organization of the workplace and the regime of the operating theatres and ending with the technical skill of the surgeon. The authors emphasize the problem of subsequent rehabilitation but do not analyze it in the present work.


[Fractures of the upper part of the femur treated by means of the Ender osteosynthesis method].

Intramedullary osteosynthesis by Ender's method proved very successful and easily managed from the technical aspect, while it causes relatively little discomfort to the patient and resolves the problem of fractures of the femur in the trochanteric area. The greatest advantages, as compared with other types of osteosynthesis, are that it is not as time consuming as other procedures, that it is a minor operation which reduces the incidence of infection and causes minimal stress to the patient. When careful anaesthesia is used, it is frequently the only operation which can be used in biologically old and high risk patients.


[Distant metastasis of malignant melanoma in the small intestine, 2 case reports].

The authors present the case history of two patients with metastases of a malignant skin melanoma into the gastrointestinal tract. One case detected on operation, with concurrent affection of the adrenal gland, the second one with the symptomatology of occult haemorrhage. The paper is supplemented by a review of the literature covering the last five years. The authors recommend in the described cases an active surgical approach.


[Reinforcement anastomoses in the small intestine with fibrin glue (experimental study)].

In an experiment on baby pigs the authors tested the strength of an end-to-end anastomosis of the small intestine by atraumatic inverted silon stitches in one layer reinforced by a fibrin film along the circumference of the suture. Intraluminal pressure was increased 15 minutes after application of the glue and completion of the anastomosis. The differences in the strength of the simple suture and that reinforced by the fibrin coagulum are statistically significant. The fibrin-reinforced anastomosis is more resistant against increased intraluminal pressure. After resection of the damaged portion the passage was restored by a new anastomosis in one layer and reinforced by fibrin glue. Five minutes after the fibrin film had dried, the loop was returned into the peritoneal cavity. All experimental animals survived without damage for a period of six months. Histological examination of the preparation confirmed satisfactory healing by a smooth scar without reaction of the tissue to alien material.


[The fibrin glue system in the care of experimental injuries of the spleen and liver].

In experiments on 28 rabbits and 28 baby pigs the authors tested the effectiveness of a fibrin glue mixture prepared from locally available components in a fatal injury of the liver and spleen. The authors used an original system of application "Duplojekt" for simultaneous application. Using the technique of digital compression of the margins of the wound and simple application of the fibrin glue, they repaired extensive tissue injury. They investigated the time needed for haemostasis, for adequate adherence of the coagulum to the wound and adequate hardness of the coagulum. They recorded the total time of the operation and amound of glue used. They used two different concentrations of fibrinogen with a low and high value and a standard concentration of thrombin for rapid reaction and formation of the coagulum. The authors found equal haemostatic effects of the two systems and different times of the mixtures with a high and low fibrinogen value. The glue with the high fibrinogen concentration was more effective. Both systems with the low and high fibrinogen concentration are, however, effective and reliable. Treatment of an extensive injury was safe in all instances. All experimental animals survived the operation, and the postoperative period and were killed at the defined times. The selected method and elaborated technique are useful for clinical surgery.


Major complications associated with extra-amniotic prostaglandin F2 alpha termination of the mid-trimester pregnancy.

Extra-amniotic prostaglandin F2 alpha (PGF2 alpha) termination of mid-trimester pregnancy can be associated with serious complications, defined for the purposes of this study as unintended major surgery or death as a result of the termination. A retrospective study of 319 such mid-trimester terminations at Johannesburg hospital revealed that 3 patients required hysterectomy, 1 developed a large tear of the posterior cervix and 1 died suddenly during the procedure. We are therefore considering changing our methods for second-trimester terminations.


Youth attending Cape Peninsula day hospitals. Sexual behaviour and missed opportunities for contraception counselling.

Questionnaires were completed by a sample of youth (aged 15-24 years) attending day hospitals in the Cape Peninsula. Of the total sample of 225, 73.3% indicated that they had experienced sexual intercourse; of these, 27.3% had had 2 or more partners in the previous year, and on their last coital episode 91.0% had known their partner for more than 7 days and 52.8% had used some form of contraception. The criteria of a strict definition of missed opportunity for contraception intervention were fulfilled by 7.6% of the total sample, while 43.6% of those who had experienced sexual intercourse and 43.9% of those who had not did not receive contraception intervention but would have liked to have done so. Those who had had more than one partner in the previous year were more likely to have satisfied the strict definition of missed opportunity, while of those who had not had sexual intercourse, younger respondents and students were more likely not to have received contraception intervention despite wanting such intervention. It is concluded that all youth attending day hospitals should routinely be offered contraception counselling and that the issue of sexually transmitted diseases should be addressed simultaneously.


Reasons for lack of condom use among high school students.

This exploratory qualitative study was undertaken to identify barriers to condom use among high school students in Natal. Phase 1, a group discussion, with 50 high school students of all races from 10 schools, revealed that 17 (34%) were sexually active, 8 (47%) of these had used a condom at least once, but none had used condoms in every sexual encounter. Phase 2 comprised 36 focus group discussions involving about 650 black high school students. These discussions confirmed the finding of phase 1 that high school students were not using condoms to any significant degree. In their opinion, condoms limited sexual pleasure, indicated a lack of trust in the partner's faithfulness, challenged the male ego, and were associated with sexually transmitted diseases. Their contraceptive properties were viewed with suspicion and considered undesirable by those teenagers who wished to prove their fertility. In addition, condom use was not sufficiently well understood and condoms were not accessible or available when required. We recommend that condom promotion strategies should include an adequate explanation of how condoms work and detailed information on their local availability. They should be available at a government-subsidised price through more accessible outlets; popular figures and recognised leaders should be encouraged to support anti-AIDS campaigns and condom use, particularly in the public media.


A community paediatric information system--a tool for measles surveillance in a fragmented health ward.

A community paediatric geographical information system using hospital-based inpatient data was created to monitor longitudinal child health trends, to define paediatric priorities and to generate research ideas and interventions in a large and very fragmented health ward. This epidemiological tool has been used to describe measles admission trends over a 4-year period (1987-1990), which included a severe measles epidemic. The examination of these trends in progressively finer geographical categories has identified a number of areas with a particularly high incidence of measles and has provided useful guidelines for subsequent community-based research. The demonstration of low vaccination coverage in areas designated as high incidence areas by this system suggests that these trends are accurate and that they can reliably be used for routine measles surveillance. The use of this system for measles surveillance on a prospective basis is expected to enable workers in this area to identify any increase in measles incidence rapidly, to pinpoint where this increase is occurring, and to make it possible to respond in a more focused manner to outbreaks when they occur.


The use of COSAS in the analysis of vaccination coverage in urban, peri-urban and rural populations in the Edendale/Vulindlela district of KwaZulu.

A repeat vaccination coverage survey has been conducted in the Edendale/Vulindlela district of KwaZulu. The survey data were processed using the Coverage Survey Analysis System (COSAS) developed by the World Health Organisation (WHO) through its Expanded Programme on Immunisation (EPI). A modified random cluster sampling method was used to select 281 children between the ages of 12 and 23 months. Of the children surveyed, 83% were in possession of Road-to-Health cards (RTHCs). The best estimate of overall coverage for doses up to and including the second doses of polio and diphtheria, pertussis and tetanus (DPT) was 85% or higher, but estimates for polio 3 and measles, at 72% and 67% respectively, remain suboptimal. Stratification of coverage into urban, peri-urban and rural categories revealed that the major contribution to the fall-off in coverage, after the second dose of polio and DPT, came from children in the peri-urban category with estimates of 52% for polio 3 and 38% for measles. The fact that coverage in the peri-urban population for doses up to and including polio 2 was 78% or higher indicated that the peri-urban influence responsible for this drop-out effect occurred between the approximate ages of 5 and 8 months. This identified populations in informal peri-urban settlements as a priority group for urgent intervention and further study. The estimation of missed opportunities at visits when vaccinations are normally given, found in this survey to occur in 17% of children, was a useful feature of COSAS and provided a basis for a specific intervention.


History of medicine. Paulesco.

Nicolas Constantine Paulesco achieved the unrecognised distinction of proving that an unknown but constituent factor of the pancreas controls the physiological value of the blood-sugar of a normal animal and that its absence is the cause of diabetes mellitus. His research in this particular field of medicine was carried out on dogs and his proof was the culmination of years of experimental work of precursors, colleagues and himself. This great advance, perhaps equivalent in some respect to the discovery of the therapeutic virtue of penicillin, remains unacknowledged. An exposition of the facts attendant upon this neglect follows. The reader is left to draw his or her own conclusion regarding the award of the Nobel Prize for Medicine in 1923.


First reported case of alpha-mannosidosis in the RSA.

The first known case of alpha-mannosidosis in the RSA is reported. Presentation was classic, viz. delayed speech, kyphoscoliosis and hearing loss at the age of 4 years. Among the generally rare inherited lysosomal storage diseases, alpha-mannosidosis is regarded in Europe and the USA as one of the more common disorders. It is suggested that the apparent underdiagnosis in South Africa may stem from lack of clinical recognition of a condition, which is relatively simple to diagnose biochemically. The clinical and radiological features of the child are described in the hope that clinicians will develop an awareness of the disorder, and include it in the differential diagnosis of deaf children who may also have mild skeletal abnormalities. Antenatal diagnosis of this untreatable condition is possible, so the birth of further affected children in a family could be prevented.


Orthotopic liver transplantation at Groote Schuur Hospital.

We present data on 10 patients (5 men and 5 women, aged 21-56 yrs) with end-stage liver disease or tumour who underwent orthotopic liver transplantation at Groote Schuur Hospital between October 1988 and June 1991. Standard surgical techniques were used for procuring the donor liver, the recipient hepatectomy and the implantation of the liver. The venovenous bypass method was used in all but 2 patients. Postoperative immunosuppression was usually achieved with cyclosporin, azathioprine and low-dose steroids. Six patients were treated with prophylactic OKT3. Rejection episodes were treated with bolus doses of intravenous steroids. The indications for liver transplantation included chronic active hepatitis progressing to cirrhosis (5), biliary cirrhosis in association with inflammatory bowel disease (1), sclerosing cholangitis (2), alpha 1-antitrypsin deficiency (1), and tumour (1). All patients with chronic liver disease had experienced at least one complication, examples of which included encephalopathy, bacterial peritonitis, ascites, variceal bleeding and septicaemia. Serious postoperative complications included acute rejection of the transplanted liver, renal and liver failure that responded to intensive care support and medical management. One patient died on the 11th postoperative day with complications of bleeding oesophageal ulcer, shock and fungaemia. The remaining patients are alive and well 1-31 months after transplantation.


Anaesthesia for liver transplantation. The Groote Schuur Hospital experience.

In October 1988 the orthotopic liver transplantation programme recommenced at Groote Schuur Hospital. The experience gained from our first 10 patients is described here. Anaesthesia for this type of surgery is demanding given the long duration of the operation and the severe haemodynamic and physiological alterations that can occur. A rapid sequence induction is usually performed and anaesthesia maintained with fentanyl and isoflurane. Dopamine and mannitol are used for renal protection. Extensive monitoring of haemodynamics, biochemistry, coagulation and temperature is essential. A rapid infusion device is mandatory as massive blood loss may occur. All patients were electively ventilated in the surgical intensive care unit postoperatively. One patient died 11 days postoperatively. The remainder are well at the time of writing.


AIDS--the Baragwanath experience. Part I. Epidemiology of HIV infection at Baragwanath Hospital, 1988-1990.

This four-part series describes the experience with HIV infection at Baragwanath Hospital to December 1990. In this first part we give an overview of the emergence of this disease and of its impact on the hospital. From July 1988 to December 1990, 426 HIV-positive individuals were identified: 58 were women identified in surveys at antenatal and gynaecology clinics, 60 were parents of infected babies or sexual contacts of hospitalised patients, and 30 were not inpatients (mainly patients at Soweto clinics). Of the 278 inpatients, 16 were identified in the latter 6 months of 1988, 54 in 1989 and 208 in 1990. Fifty-one per cent of the patients were in the adult medical wards, 11% in surgery, 20% in paediatrics and 18% in other disciplines. One per cent of sera from Wassermann reaction-positive women in mid-1990 were HIV-positive; this also applied to 1% of antenatal women in late 1990 and 2.7% of women with pelvic inflammatory disease. The HIV antigen assay is a useful adjunctive assay in the evaluation of HIV-antibody-positive children. The false/true-positive ratio of a rapid HIV antibody test was 2:1 initially, but the specificity improved with experience. The use of rapid diagnostic assays for HIV must be restricted to laboratories with experience in reading assays and where definitive follow-up testing is assured.


AIDS--the Baragwanath experience. Part II. HIV infection in pregnancy and childhood.

By the end of 1990, 51 symptomatic children with perinatally acquired HIV infection had been admitted to Baragwanath Hospital. Of 42 children who were followed up for at least 3 months, 15 (35.7%) died and 16 (38.1%) were lost to follow-up. The case fatality rate for these children lies between 35.7% and 73.8%. Most children became symptomatic before the age of 6 months and presenting features seen in over 70% of cases included lymphadenopathy, failure to thrive and hepatomegaly. Surviving children had recurrent admissions to hospital, predominantly for respiratory distress. Many had bacterial pneumonias. Cardiac involvement (cardiomyopathy and cor pulmonale), recurrent serious bacterial infections and neurodevelopmental abnormalities were common. Our experience confirms that vertically acquired HIV infection has a relatively short incubation period and progresses rapidly with cardiorespiratory symptoms predominating. Five HIV seroprevalence studies have been conducted in pregnant women attending Baragwanath Hospital and the Soweto clinics since 1988. The calculated doubling time is between 7 and 21 months. At the end of 1990 the HIV seroprevalence rate in pregnant women was 0.82% (95% confidence limits 0.44-1.19%).


AIDS--the Baragwanath experience. Part III. HIV infection in adults at Baragwanath Hospital.

By December 1990, 181 HIV-positive black adults had been seen in the medical wards and HIV clinic at Baragwanath Hospital. Fifty per cent were in the late stage of HIV infection; 34% of those so diagnosed in 1990 have died. Equal numbers of both sexes have been seen. Their ages have ranged from 16 years to 66 years, with peak frequencies in women aged 20-29 years and in men aged 30-39 years. Tuberculosis was the commonest complicating infection, followed by acute pneumonia. Pneumocystis carinii pneumonia was rare. Herpes zoster was the first sign of HIV infection in 13% of clinic patients. 'Slim disease' occurred in only 11% of patients, a much lower figure than in other parts of Africa.


AIDS--the Baragwanath experience. Part IV. Counselling and ethical issues.

This fourth part of the series describes the setting up of counselling for HIV-positive patients in response to the need at Baragwanath Hospital. Nurse counsellors were trained and supervised. The work, extending over 2 1/2 years, raised a number of issues for patient care and also for wider community education. Brief reference is made to pertinent ethical and cultural issues.


Intracranial cryosurgery in a canine model: a pilot study.

Although virtually abandoned decades ago following the introduction of levodopa for the treatment of movement disorders, intracranial cryosurgery potentially offers a simple and accurate means of destroying deep-seated lesions when coupled with computed tomographic-stereotaxic placement techniques. We performed a pilot investigation of the size and histology of brain cryolesions in six dogs, using a 3-mm probe maintained at -160 degrees C for 6 minutes while simiultaneously monitoring the process by real-time ultrasound. Lesion diameter was 1.4 +/- 0.1 cm at less than or equal to 2 days but enlarged to 2.25 +/- 0.21 cm at 1 week, primarily at the expense of white matter. Ultrasound appearance of the lesion was characterized by a hyperechoic ice ball, the size of which consistently underestimated true size (determined by histology). By microscopy, the lesion was a hemorrhagic infarction that incited little surrounding edema and exhibited a sharp transitional zone. These data indicate that the cryosurgical probe can lesion significant volumes of brain in a reproducible and discrete fashion with minimal reaction to the surrounding tissue. Further work is required to clarify the observed "growth" of lesion size between days 2 and 7.


Suprasellar xanthomatous Rathke's cleft cyst.

A case of a symptomatic suprasellar Rathke's cleft cyst in a 35-year-old woman is presented. The cyst wall and contents showed large collections of xanthomatous cells. With the exception of a few pituitary hormone-positive cells, immunohistochemical and ultrastructural features of the lining epithelium in this case of Rathke's cleft cyst were indistinguishable from colloid cysts of the third ventricle with similar secondary changes.


Use of allopurinol and deferoxamine in cellular protection during ischemia.

During cellular ischemia and death, many changes occur in the cell. These include the build-up of purines and lipid peroxidation. In this study, we evaluated the effectiveness of allopurinol, which blocks purine breakdown, and deferoxamine, which inhibits lipid peroxidation, as cytoprotective agents. Rats were subjected to middle cerebral artery occlusion and were treated with high or low doses of allopurinol or high or low doses of deferoxamine, with normal saline used as a control. Treatments were given 1 hour before, 1 hour after, or 5 hours after occlusion. The outcome was based on neurological status and infarct size. Both infarct size and neurological status were found to be improved in all treatment groups when compared to controls. This study suggests that the use of these agents prevents cellular damage during ischemia.


Intracranial germ-cell tumor with synchronous lesions in the pineal and suprasellar regions: report of six cases and review of the literature.

The features of intracranial germ-cell tumor with synchronous lesions in the pineal and suprasellar regions (GCTSPS) in six patients were investigated. GCTSPS accounted for 12.8% of all germ-cell tumors (GCT) in our brain tumor study group. In all cases, the initial symptoms were attributable to the suprasellar lesion, and symptoms due to the pineal GCT developed only after admission. Five of the six cases were histologically diagnosed as germinoma. In all cases, tumors of both regions disappeared after irradiation, resulting in no recurrence for an average of 55.3 months. Our experience and reports in the literature suggest that GCTSPS is highly sensitive to radiation in most cases, although some reports indicated that recurrence is frequent after radiation therapy alone. It is suggested that histological diagnosis in one of the GCTSPS lesions is undertaken to make a plan for the following treatment.


Multiple intracerebral arteriovenous malformations: report of three cases and review of the literature.

Multiple intracerebral arteriovenous malformations are thought to be exceedingly rare lesions and have usually been reported as single cases. During the past 2 years, we have treated three patients with multiple cerebral arteriovenous malformations, representing 3.2% of a consecutive series of 95 arteriovenous malformation patients seen since 1976. Details on 17 other cases are available in the literature and are summarized here. The incidence of multiple arteriovenous malformations in major series ranges from 0.3% to 3.2%; the average incidence is 1.9% based on 21 cases encountered in a total population of 1102 arteriovenous malformation patients. Patients with multiple arteriovenous malformations often have other vascular anomalies of the brain or soft tissues, but the clinical mode of presentation, age, sex, and anatomical distribution of the lesions are the same as those of patients with single arteriovenous malformations. The use of four-vessel angiography in combination with magnetic resonance imaging may result in a higher detection rate for such cases.


Association of primary intraspinal meningiomas and subcutaneous meningioma of the cervical region: case report and review of literature.

A report is made of a unique combination of occurrences of primary intraspinal epidural and subdural meningiomas and primary subcutaneous meningioma in the cervical region of a 15-year-old boy. The subcutaneous meningioma was detected at birth. Review of 92 recorded cases of primary dermal meningiomas revealed that they tended to occur in young patients, with an average age of 34 years for both sexes. The female-to-male ratio was 4:5. Most cutaneous meningiomas occurred in the head and neck, and the scalp was the most common site.


Unexpected movement disorders in neurosurgical practice: report of three cases.

Hyperkinetic movement disorders may develop as a complication of stereotactic thalamotomy or pallidotomy. However, such movement disorders are uncommon after nonsterotactic intracranial operations. The authors report three cases of involuntary movement disorders unexpectedly developing after intracranial operations. The patients had undergone clipping of an internal carotid aneurysm, removal of an intracerebral hematoma, and resection of a tentorial meningioma. Two patients developed choreic movements and a dystonic posture of the unilateral upper extremity. One patient showed a tremor that had features of both parkinsonism and essential tremor. The symptoms of these patients were medically uncontrollable, and they were successfully treated with stereotactic ventrolateral thalamotomy.


Central neurocytoma presenting with gigantism: case report.

We report a case of central neurocytoma presenting with gigantism. The patient was a 19-year-old man with a 2-year history of rapid growth. Computed tomography revealed a round, slightly enhancing calcified tumor in the septal region. This lesion was resected, and postoperative radiotherapy was given. The preoperative serum growth hormone level was 20.7 ng/mL, and postoperatively this fell to 0.9 ng/mL. Pituitary dysfunction was not noted either before or after the operation. A low level of production of growth hormone releasing factor was detected when tumor cells obtained during surgery were cultured.


Aspergillotic aneurysm formation of cerebral artery following neurosurgical operation.

A rare case of intracranial aspergillotic aneurysm following neurosurgical operation for facial spasm is presented. Severe meningitis had persisted several days prior to the subarachnoid hemorrhage which occurred on 70th postoperative day. Angiography demonstrated a fusiform aneurysm at the peduncular segment of the superior cerebellar artery on the other side of operation. As the repeated cultures of CSF were negative, the pathogenetic factor causing aneurysm formation could not be identified before second operation of aneurysmal resection. Pathological study of the specimen revealed the arterial wall being deeply invaded by aspergillotic hyphae.


Traumatic occipital condyle fracture, multiple cranial nerve palsies, and torticollis: a case report and review of the literature.

A 32-year-old man sustained a unique combination of injuries: an occipital condyle fracture, left tenth to twelfth cranial nerve palsies, and chronic torticollis secondary to atlantoaxial rotatory fixation. Computed tomography (CT) demonstrated a triangular fragment of bone in the posterior fossa, and three-dimensional CT-reconstructed images confirmed the bone fragment to be from the occipital condyle. The patient made a good recovery with conservative management. Few occipital condyle fractures have been reported, and they should be suspected in patients who sustain painful neck and lower cranial nerve palsy following trauma. CT and plain films are complementary in confirming the diagnosis.


Superselective embolization of spinal arteriovenous malformations using the Tracker catheter.

Eighteen patients with spinal arteriovenous malformations had been treated with conventional embolization, surgical removal, feeder ligation, and/or feeder coagulation between February 1985 and March 1990. The lesions included six glomus, four juvenile, three extramedullary, and five dural arteriovenous malformations or fistulas. Embolic therapy was conducted in 14 patients by introducing the tip of a catheter into the segmental arteries and injecting polyvinyl alcohol strips (500-1000 microns) (conventional embolization). Follow-up spinal angiography disclosed recanalization in 10 patients (71.4%) and the appearance of new feeding arteries in five patients (35.7%). We introduced the Tracker vascular access system in April 1990. Eight patients (four glomus, one juvenile, and three dural arteriovenous malformations) were treated with the minicatheter and Ivalon particles (150-350 microns). Five patients showed neurological improvement immediately after treatment. The other three patients had severe paraparesis before treatment and did not show any improvement. One patient with a glomus-type arteriovenous malformation showed transient neurological deterioration just after embolization with the Tracker-10 to occlude a lesion fed by the posterior spinal artery, because the Ivalon particles migrated into the anterior spinal artery via the anterior spinal canal artery. In one patient with a juvenile arteriovenous malformation, the Tracker-18 catheter perforated the radiculomedullary artery originating from the right vertebral artery, and subarachnoid hemorrhage occurred. However, the Tracker-10 could later successfully occlude the arteriovenous malformation. The rates of recanalization and appearance of the new feeding vessels were 4/8 (50.0%) and 2/8 (25%), respectively.


Long-term follow-up of radiosurgically treated arteriovenous malformations in children: report of nine cases.

Long-term follow-up results of nine children treated for cerebral arteriovenous malformation with a gamma unit are presented. Complete nidus obliteration was angiographically confirmed in six cases and significant decreases in arteriovenous malformation size were observed in the other three. There were no radiation-related deteriorations in physical or mental development. In seven patients who underwent endocrinological examination more than 3 years after irradiation, five were normal and the other two showed only low serum adrenocorticotropic hormone levels, which, however, did not necessitate replacement therapy. Neurodiagnostic imaging follow-up studies revealed no radiation-induced lesions in any of the nine cases.


[The role of immune complexes in chronic liver diseases and their dynamics during treatment].

Chronic liver diseases are marked by a well-defined relationship between the intensity of the cytolytic syndrome and the level of circulating immune complexes (CIC). The highest damaging action on hepatocytes is produced by medium-sized CIC because of their penetrating and complement fixing effects. The level of thrombocytopenia and, to a less measure, of leukopenia also depends on the concentration and size of CIC in CAH and liver cirrhosis (LC), which may provide indirect evidence of the lytic action of CIC on hepatocytes, leading in turn to the impairment of microcirculation and aggravation of hepatocyte hypoxia. The data obtained attest to the role CIC of varying size play in the pathogenesis of CAH and LC. The changes in the properties of immune complexes induced by the derangement of cellular membranes also influence the course of immune responses, favouring an increase of antibody formation. As a result of an appreciable suppression of antibody and medium-sized CIC formation enhancing the cytolytic syndrome, the preference during glucocorticoid treatment should be given to the use of the medium doses of prednisolone which ensure less intensity and less duration of cytolysis as compared to the application of large drug doses.


Fundus hemorrhages in infancy.

The anatomical location and appearance of retinal hemorrhages in the infant provide important clues in the diagnosis of underlying disorders. While neonatal retinal hemorrhages related to birth trauma are common, benign, and self-limited, other retinal hemorrhages in infancy may signify intracranial aneurysms, accidental or non-accidental injury, and a variety of ocular (e.g., Coats' disease, PHPV, ROP, retinal dysplasia, hypertension, myopia) or systemic disease (e.g., hematologic or cardiovascular disorders, infection, protein C deficiency). In this review, retinal hemorrhages are illustrated and classified according to location, appearance, and etiology. Prompt diagnosis of retinal hemorrhages in infants is crucial, because treatment may be required to prevent early deprivation amblyopia and blindness. Ophthalmological findings may also be a valuable contribution to the overall medical evaluation of the infant.


[The importance of immunogenetic studies in Itsenko-Cushing disease combined with other endocrine diseases].

Ninety-seven patients suffering from Itsenko [correction of Icenko]-Cushing disease were examined. Analysis was made first of all of the clinical and laboratory signs pointing to the presence of other endocrine diseases to distinguish two groups of patients. The first group included subjects who did not manifest any concomitant diseases. The number of men and women was the same. The second group was made up of patients with associated Itsenko [correction of Icenko]-Cushing disease and other endocrine diseases. In this particular group, women were predominant. The first group patients demonstrated the predominance of the DR7 incidence, the second group that of the DR5. The method of estimating HLA associations identified is proposed. It allows distinguishing specific and nonspecific associations. In Itsenko [correction of Icenko]-Cushing disease, DR7 association is specific, whereas B8 and DR5 associations are unspecific. A specific polyendocrine autoimmune syndrome associated with Itsenko [correction of Icenko]-Cushing disease was revealed. A concept of the pathogenesis of Itsenko [correction of Icenko]-Cushing disease is advanced.


[The characteristics of the clinical course of lymphosarcomas when using combined therapy including splenectomy].

The authors relate the results of a clinico-morpho-instrumental analysis of the clinical course of lymphosarcomas in 38 patients with different morphological patterns of the disease with primary injury to the spleen. The patients received multimodality therapy including splenectomy. It has been established that later the short-term effect of splenectomy permits the implementation of different polychemotherapy programs, favouring a better lymphosarcoma prediction.


[The metabolic effects of glucocorticosteroids in patients with chronic obstructive bronchitis].

The purpose of the study was to examine the effect of glucocorticosteroids on metabolic processes that occur in alveolar macrophages and bronchoalveolar liquid in patients with chronic obstructive bronchitis, in particular the activity of the antioxidant defense system, processes of hydrogen peroxide generation, and the content of phospholipids. It has been discovered that in patients suffering from chronic obstructive bronchitis, glucocorticosteroids suppress hydrogen peroxide production and exert a negligible effect on the antioxidant system of alveolar macrophages as well as stimulate the synthesis of phospholipids in pulmonary tissue and suppress phospholipase A2 activity. To prevent unfavourable metabolic effects of glucocorticosteroids, antioxidants and stimulants of phagocytosis can be applied.


Sudden visual loss with slow recovery.

A 58-year-old healthy man presented with a history of monocular visual loss with incomplete recovery. The differential diagnosis, evaluation, and possible therapeutic interventions are discussed. The presenter controversially felt that although the source of embolic material was likely ipsilateral carotid artery and no evaluation was necessary.


Theodor Leber: a founder of ophthalmic research.

Theodor Leber became famous for his dissertation on the ocular circulation in 1865 at the youthful age of twenty-five. He was Professor of Ophthalmology at Goettingen between 1870 and 1890 and at Heidelberg University between 1890 and 1910. By presenting his original descriptions of the disorders that bear his name, this article commemorates the death, seventy-five years ago, of a founder of ophthalmic research.


[Peptic ulcer combined with other pathology. The clinical manifestations, course and therapy].

The author describes and classifies the most frequently occurring combinations of peptic ulcer and pathology of other organs and systems on the basis of examining more than 2,000 patients. Diseases and syndromes associated with peptic ulcer are distributed into 2 groups: within the gastrointestinal tract and outside it. The former ones include cardia insufficiency, deranged bowel function, rectal syndrome, diseases of the gallbladder, pathology of the liver and pancreas; among the latter ones are essential hypertension, atherosclerosis, coronary heart disease, chronic nonspecific pulmonary diseases, and diabetes mellitus. Different pathogenetic relations and clinical load are shown to exist between the underlying disease and concomitant illnesses. Evidence is provided for the concept of enlarged spasms (phenomenon of the spastic dominant) common to peptic ulcer. Efficient methods of the individualized treatment of patients with concomitant pathology are described.


Recognizing and managing the litigious patient.

There is no accurate pre-treatment profile of the litigious patient. It is usually the lawsuit-causing physician who drives the patient to initiate litigation. The establishment and control of the physician-patient relationship are the keys to preventing litigation; this is achieved by improving physicians' ability to communicate, demonstrate empathy and support, and conduct appropriate discussion of informed consent. After treatment, physicians must pay special attention to patients who exhibit certain behavior typical of dissatisfaction. They should be accorded extra time and attention and, in some instances, should be referred to another practitioner for a second opinion and follow-up care.


[The diagnosis of cancer of the stomach and large intestine under active dispensary observation].

Among patients placed under permanent medical observation carried out for 6-8 years, gastric carcinoma (GC) was revealed in 288 and colonic carcinoma (CC) in 377 cases. In 67 and 60% of the patients, respectively, the diagnosis was established as a result of systematic dispensary examinations. The first and second stage disease was identified in 50 and 43% of the cases, including 67% of GC and 62% of CC patients undergoing active examinations. In 40% of the cases on the average, the disease may run an asymptomatic course, including the late stages of the disease. In half the patients, the clinical manifestations did not last more than 3 months, with their duration being independent of the disease stage. It is assumed that at the initial stage the tumor may, during a short period of time, reach the size corresponding to both early and late stages of the disease, after which the rate of tumor growth is likely to be slower. The authors document the necessity of a comprehensive approach to the diagnosis of GC and CC, using the whole armamentarium of classical and up-to-date methods.


[Unconjugated hyperbilirubinemia in young people].

Altogether 64 young patients with nonconjugated hyperbilirubinemia (NH) underwent clinico-morphological correlations to establish the nosological essence of pigment metabolism disorders revealed. 32 patients showed up the signs of chronic nonspecific hepatitis, including 7 patients with the signs of chronic aggressive hepatitis. The remainder 15 patients were found to have other inflammatory processes in the liver. Only 10 persons examined (15.6%) were diagnosed to have functional hyperbilirubinemia and 7 (10.9%) to have latent hemolytic anemia. The conclusion is made about the necessity of a comprehensive examination of young persons with NH. The morphological examination of the liver is a must to early verify the pathological process manifested by the impairment of pigment metabolism.


[The clinical significance of immunodeficiency states in patients with viral hepatitis B].

Examination of 374 patients with acute viral hepatitis B made it possible to unravel certain mechanisms of the development of secondary immunodeficiency in the T immunity system: hypoxia and hypoxemia, activation of lipid peroxidation, suppression of antioxidant activity of blood serum, derangement of the synthesis of free radical forms of oxygen by mono- and polynuclear cells and ATR deficiency in them, disturbance of the interferonogenesis and synthesis of cyclic nucleotides, suppression of metabolic activity of immunocompetent cells. The character and intensity of immunodeficiency states underlie the formation of different clinical forms of viral hepatitis B.


[Laser flow cytometry in the diagnosis of chronic hepatitis of different etiologies].

A study was made of the immune status in patients suffering from chronic hepatitis (CH) of viral, alcoholic and toxic etiology. The T-system cellular immunity (OKT-3+, OKT-4+, OKT-8+, OKT-11+) was subjected to a subpopulation analysis using monoclonal antibodies and flow laser cytometry. CH of varying etiology is marked by impairment of the immune status. Especially manifest are suppression of OKT-3(+)-, OKT-4(+)-, OKT-8(+)-positive cells and imbalance of OKT-4+ and OKT-8+, with the changes revealed being dependent on the etiological pattern of CH. The data obtained point to the development of secondary immunodeficiency of the T-cell component at the level of different T lymphocyte subpopulations, which depends on the clinico-morphological and etiological pattern of CH. The revealed changes in the immune system may serve as a criterion for differential diagnosis and elaboration of efficient immunocorrective therapy of CH.


[The immunomodulating and hepatotropic effect of correcting hyperprolactinemia and hypophyseal gonadotropic dysfunction in liver cirrhosis patients].

Men suffering from liver cirrhosis were examined. They demonstrated a decrease in the blood content of gonadotropic hormones and testosterone and a rise of estradiol and prolactin. The changes indicated were more pronounced in decompensated liver cirrhosis and were associated with lipid peroxidation activation and a reduction of the count of T suppressor lymphocytes. As a result, the treatment of men suffering from decompensated liver cirrhosis and hyperprolactinemia by parlodel lowered blood prolactin and activity of lipid peroxidation. The use of chorionic gonadotropin for the treatment of men with decompensated liver cirrhosis and a low content of blood lutropin produces an immunomodulatory effect. Parlodel and chorionic gonadotropin favour a decrease of the cytolytic syndrome.


[The immunological indices in inflammatory and tumorous diseases of the pancreas].

Nineteen patients with pancreatitis and 40 with pancreatic carcinoma were examined for certain immunological characteristics (immunoglobulins, immune complexes, PHA-induced lymphocyte proliferation) and for the level of carcinoembryonic antigen (CEA) and CA 19-9 depending on blood bilirubin. Hyperbilirubinemia was identified in 21 patients with carcinoma and in 3 suffering from pancreatitis. Both patients' groups manifested an increase of the IgA level. Especially high characteristics were seen in hyperbilirubinemia. The level of other class immunoglobulins and immune complexes did not depend on blood bilirubin. The patients demonstrated suppression of PHA-induced lymphocyte response by autologous plasma, with more remarkable suppression being observable in hyperbilirubinemia. The level of CEA or CA 19-9 was increased in 89% of the patients with pancreatic carcinoma and in 30% of pancreatitis patients. No relationship was recorded between the level of oncofetal antigens and blood bilirubin.


[Cholecystokinin incretion and the pharmacological effects on it in patients with chronic pancreatitis].

In patients with chronic pancreatitis (CP) (cholepancreatitis and primary recurrent pancreatitis), a moderate decrease of urocholecystokinin (UCK) excretion as a criterion for incretion of cholecystokinin-pancreozymin (CK) by duodenal endocrine cells was recorded in the presence of concomitant atrophic duodenitis. The beta-adrenoblocker obsidan, the blocker of m-cholinergic receptors gastrozepin, the antagonist of calcium channels finoptin and the synthetic analog of endogenous opiates dalargin reduced excretion of UCK in CP exacerbation. The decrease of CK incretion can be viewed as one of the mechanisms of the therapeutic action of these drugs in CP exacerbations. In the stage of CP remission, calcium gluconate consistently increased basal and intraduodenal oil (as a realizer of CK incretion) infusion-stimulated excretion of UCK. The enhancement of duodenal incretory activity is an essential mediating mechanism by which calcium gluconate stimulates pancreatic enzyme excretion.


[The pathogenetic problems of gastric and duodenal peptic ulcer].

Studies into the content of nonspecific defense factors, secretory and serum immunoglobulins in blood and biological fluids (saliva, gastric juice, duodenal contents) in patients suffering from peptic ulcer have demonstrated significant changes in local and general immunity. Exacerbation of the disease was marked by a decrease of the titer of complement, C3-component of complement, and lysozyme level. At the same time there was an increase of the concentration of secretory immunoglobulins and immunoglobulins in blood serum and external secretions. The data obtained attest to the tension of humoral immunity and nonspecific defense in peptic ulcer patients, giving rise to the consideration of the changes in the humoral component as one of potential mechanisms by which ulcer is formed.


[The characteristics of duodenal peptic ulcer in obese persons].

Analysis was made of the rate of clinical manifestations and complications in 77 patients with overweight exceeding stage I obesity, suffering from duodenal ulcer. In the overwhelming majority of the patients, the disease ran with typical complaints and the diagnosis of peptic ulcer was not difficult. In subjects prone to and suffering from obesity, duodenal ulcer accounted for 2.3% among all the patients with duodenal ulcers. The patients were noted to be fairly prone to complications, particularly to the stenosing of the duodenum. Concomitant complications occurred frequently enough (36.3%). In obese patients, nontypical "low" localization of duodenal ulcer and a high proneness to hypersecretion were encountered more frequently.


[The diagnostic value of the histamine test in studying the gastric juice of patients with duodenal peptic ulcer].

Measurements were made of the content of pepsin and hydrochloric acid in gastric juice from 96 duodenal ulcer patients, obtained under the conditions of basal secretion and after histamine administration in the submaximal dose. The disease was marked by changes in the response to histamine on the part of gastric glands. In duodenal ulcer patients, histamine primarily stimulates pepsin secretion whereas in healthy subjects, secretion of hydrochloric acid is predominant. Based on the regularity thus revealed, a new test (the ratio of the histamine index of pepsin to the histamine index of hydrochloric acid) was developed. This test is of importance for the diagnosis of duodenal ulcer and predicting the gravity of the course it may run.


[The differentiated treatment of patients with duodenal peptic ulcer].

There were 45 patients suffering from duodenal ulcer in the stage of exacerbation and 15 subjects who served as control. Radioimmunoassay and immunomorphological PAP methods were used to examine the blood PGI and gastrin levels, the number of gastroduodenal G and D cells, the characteristics of basal and stimulated acid production in gastric juice in the treatment with gastrozepin (22 persons) and ranisen (23 persons). Depending on the concentration of gastrin in the blood and the number of pyloric G cells, the patients were distributed into two groups: with hypergastrinemia and/or hyperplasia of G cells (48%) and with normogastrinemia and the normal number of these cells (52%). It has been shown that the continuous treatment with gastrozepin of the patients with hypergastrinemia and/or hyperplasia of pyloric G cells was followed by the normalization of blood gastrin concentration and of the number of pyloric G cells; on the contrary in the patients with normogastrinemia and the normal amount of these cells, the analogous characteristics remained unchanged. After the treatment with ranisan the patients with normogastrinemia and the normal amount of pyloric G cells manifested hypergastrinemia without any changes in the amount of G cells; meanwhile in the patients with hypergastrinemia and/or hyperplasia of G cells, the analogous characteristics were unchanged. In these groups patients, the rate and the times of the relapse occurrence were different throughout the whole year. The data obtained support the nonuniformity of duodenal ulcer.


[The dynamics of the indices of protein metabolic homeostasis and the status of duodenal mucosal regeneration during the etaden treatment of duodenal peptic ulcer].

The authors relate the results of examining 149 men suffering from duodenal ulcer. The main group was made up of 75 patients given parenteral etaden treatment combined with conventional therapy. A study was made of the dynamics of clinical manifestations, the level of total protein and its fraction in the blood, protein metabolism (by radionuclide technique). Pieces of the duodenal mucosa from the periulcerous area were examined under microscope. Scanning and electron microscopy was also performed. Based on the data obtained it is concluded that etaden had active influence on protein synthesis, which favoured more rapid regression of the ulcerous defect in the main group patients. Morphological studies have also shown the positive dynamics of the regenerative process.


[The effect of hyperbaric oxygenation on the secretory, motor function and microcirculation of the stomach and duodenal walls in patients with duodenal ulcers].

A total of 22 patients with duodenal ulcer were examined for secretory and motor functions, microcirculation of the gastroduodenal wall and changes in the stomach-duodenum interrelations under the influence of hyperbaric oxygenation. Of these, group I included 9 patients with active ulcer; group II 13 persons with a healing ulcer. To assess gastric and duodenal functions, use was made of pH-metry combined with the measurement of intraluminal pressure by "open catheters". Microcirculation of the gastroduodenal wall was estimated by the radiation method. The studies have shown that the patients with active ulcer treated by hyperbaric oxygenation manifested a decrease of motor activity of both stomach and duodenum, an improvement of acid-neutralizing function of the stomach, a reduction of the duration of duodenum acidification, a greater normalization of microcirculation in the duodenal wall than in the gastric wall. In the patients with healing ulcers, the duodenal motility returned to normal, the initially elevated gastric motility fell to normal, the acidification of the duodenal bulb declined, and the regional blood flow returned to normal. It may thus be concluded that the positive impact of hyperbaric oxygenation on gastroduodenal function was more pronounced in the patients with healing ulcers where a more considerable decrease of motor activity was not accompanied by duodenal motility suppression.


[The clinico-pathogenetic variants of cholestasis in different liver diseases].

To base the clinico-pathogenetic nonuniformity of cholestasis in different liver diseases, 135 patients distributed into groups were examined. Group I was made up of 48 patients with chronic persistent hepatitis, group II of 34 patients with chronic active hepatitis, group III of 29 patients with liver cirrhosis, and group IV of 24 patients with primary and metastatic liver carcinoma. The data obtained suggest the existence of different forms of cholestasis: multicomponent cholestasis, partial bilirubin cholestasis, partial choleacid cholestasis. In the group I patients, the incidence of cholestasis was 8.3%, in group II 2.9%, in group III 3.4%. The incidence of partial choleacid cholestasis was 4.2% in group I, 2.9% in group II, and 6.9% in group III. The presence of partial cholestasis may be caused by the impairment of the assumed "personal" carrier for different bile components.


[Chronic gastritis from the aspect of a thrombohemorrhagic syndrome].

As many as 148 patients were examined to demonstrate that chronic gastritis (CG) runs its course in the presence of marked changes in microcirculation and hemostasis which go into the framework of the chronic recurrent thrombohemorrhagic syndrome. The manifestations of the latter one were more appreciable in a dramatic exacerbation of the disease, erosive gastritis, diffuse atrophy of the mucous membrane and secretory insufficiency of the stomach, and disease standing over 10 years. The disorders indicated are involved into the pathogenesis of CG and promote the development of morphofunctional alterations in the gastric mucosa.


[Functional intestinal dyskinesias].

The authors relate the results of examining 120 patients with functional disorders of the colon. The majority of the patients manifested diverse mental abnormalities of the neurotic origin, represented by different patterns of mental pathology, somatized disturbances, neuroses and psychopathies. The conditions favouring the origin of neurotic and functional disorders have been elucidated. It is concluded from the comparison of different treatment modalities that psychotherapy may be preferred.


[The processes of mono-, bi- and polysubstrate digestion in chronic enteritis].

Forty-six patients suffering from chronic enteritis (CE) and 34 healthy subjects were examined for the effect of standard polysubstrate food (protein plus fat plus carbohydrate). It has been shown that in the healthy subjects, addition of protein food exerted a stimulating effect on enzymic and absorption functions of the small intestine whereas fat intake produces a reverse, inhibitory effect. As a rule, in small intestinal lesions that effect is retained. However, there was a significant reduction of the hydrolysis and absorption of both monosubstrate and bi- and polysubstrate food. It should be stressed that in CE patients, the use of polysubstrate food results in its better assimilation as compared to monosubstrate food substances.


[Gluten enteropathy].

The authors relate the results of 10 years of observations of 113 patients suffering from gluten enteropathy (GE) of the adults. In all the patients, the diagnosis was supported by the presence of hyper-regenerative atrophy of the small intestinal mucosa (total in 70% and subtotal in 30%). Metabolic disorders and cellular immunity were investigated. At the onset of the observations 70.7% of the patients demonstrated malabsorption, stage III gravity, and 29.3% stage II. It has been proved that permanent and strict adherence to the agluten diet and administration of corticosteroids in the most severe cases in combination with pathogenetic therapy of diarrhea and metabolic disorders permit attaining a steady clinical remission, improvement of normalization of the biochemical and immunological characteristics, a tendency toward normalization of the small intestinal mucosa, and even the recovery of its normal structure in part of the cases.


[The function of the small intestine based on hydrogen test data in men who have been exposed to small doses of ionizing radiation in the cleanup of the sequelae of the accident at the Chernobyl Atomic Electric Power Station].

Sixty-seven participants of the elimination of Chernobyl accident sequels were examined. Of these, 30 persons (44.8%) showed normal characteristics of the three small intestinal functions studied: activity of the intestinal enzyme beta-galactosidase, motility and microbial dissemination, 23 (34.3%) deficiency of the intestinal enzyme beta-galactosidase, and 24 (35.8%) bacterial dissemination of the small intestine. In 12 persons (17.9%), the deficiency of beta-galactosidase was associated with dysbiosis of the small intestine. The incidence of hypolactasia did not exceed the characteristic typical on the whole of the population of the Moscow region.


[Errors in the diagnosis of diseases of the large intestine].

The quality of the diagnosis of colonic diseases was analyzed in 395 patients. Comparisons were made of the diagnoses on admission to and discharge from hospital: in irritated colon and its dyskinesias, ulcerous colitis and Crohn's disease, carcinoma, polyps, other forms of colitis and so forth. Errors in the basic diagnosis constituted 51.0 +/- 1.8%; including 25.4 +/- 1.6% of cases of overdiagnoses; in 25.6 +/- 1.6%, the disease was not recognized. The main colonic diseases were coupled with other intestinal diseases in 42.3 +/- 2.5%, with other diseases of the alimentary organs in 37.2 +/- 2.5% of cases. The quality of the diagnosis is affected by wrong medical thinking, insufficient application of colonoscopy as well as polymorbidity of modern patients, growing with their age. Approaches to the improvement of the quality of the diagnosis of colonic diseases are determined by the causes and mechanisms of the errors made.


[Destabilization of the immune homeostasis in patients with nonspecific ulcerative colitis of varying degrees of severity].

As a result of evaluating immune homeostasis in patients suffering from nonspecific ulcerous colitis, the predictors of the patient's gravity have been established. They include: 1) phagocytic activity; 2) changes in bioenergetic processes of the cells; 3) redistribution of functional activity and its phenotypic expression among lymphocytes; 4) imbalance of humoral factors of immunity; 5) augmentation of anemia with decreased or increased iron content.


[The possibilities for the early diagnosis of ankylosing spondylarthritis].

Soluble antigen HLA-B27 was assayed in blood serum of 30 patients afflicted with ankylosing spondyloarthritis (AS) and 25 healthy subjects having HLA-B27 (B27+) antigen in the phenotype. As compared to B27+ healthy subjects, B27+ patients with AS demonstrated a significantly higher level of soluble HLA-B27 antigen. A substance whose functional activity was found to be identical to that of soluble HLA-B27 antigen in blood serum of B27- patients with AS was discovered for the first time. It was absent from B27- healthy subjects. In addition to the identification of the fixed forms of soluble HLA-B27 antigen, the assay of this antigen in blood serum enhances the potentialities of laboratory diagnosis of AS, which plays an important role at the early disease stages.


[The use of radiothermometry in patients with rheumatoid arthritis].

As a result of the work carried out, one could decide some problems: to develop standardized points of measuring temperatures of the deep structures of the joints using radiothermography, to establish for the first time the normal radiothermographic values of the temperatures for different joint groups, to recommend radiothermography as an adjuvant method for revealing early signs of the activity of rheumatoid arthritis (RA) associated with OA. Radiothermography is a convenient, cheap, available and an informative enough method, fit for the use in clinical practice to improve the diagnosis and treatment of RA.


[The metabolic characteristics of nonesterified fatty acids in the myocardium of patients with paroxysmal tachycardias and their pathogenetic role in the origin of the heart rhythm disorders].

Twenty-one patients suffering from paroxysmal tachycardia (PT) were examined for metabolism of nonesterified fatty acids (NEFA) in the myocardium as well as for interrelations with the parameters of clinical electrophysiology. It has been shown that the main features of NEFA metabolism in the myocardium of RT patients lie in their high concentration in arterial blood and in the blood of the coronary heart sinus and in their high ratio of extraction by the myocardium both in the presence of sinus rhythm and during RT, which is of the pathogenetic importance in the origin of heart rhythm disturbances. NEFA exert different effects on the antegrade and retrograde (functional and effective) refractory periods of different parts of the conduction system of the heart, favouring the onset of their electrophysiological heterogeneity.


Prevalence of inhibitors in a population of 3435 hemophilia patients in France. French Hemophilia Study Group.

A cooperative study between the 37 centers of the French Hemophilia Study Group was undertaken to establish the prevalence of inhibitor patients in the French hemophilia population. The prevalence reported in the literature varies widely from 3.6% to 17.5%. Some of the studies are dealing with a small number of patients and inhibitor patients are reported either to the total number of hemophiliacs or to the severely affected ones. The French study provided information concerning 3,435 hemophiliacs and showed a prevalence of 6.2% for the overall population. Prevalence of inhibitors was found to be 7% in the population of hemophilia A patients and 12.8% in the population of severely affected ones. The prevalence of inhibitors in the population of hemophilia patients was 2% and 4% in the population of severely affected hemophilia B patients. The cooperative study also showed that 47.5% of inhibitors are detected before 10 years of age and that 82% of inhibitor patients are high responders. Analysis of inhibitor detection in patients under the age often showed that there was a peak in the population of 2 years old children. Although not comparable to the present study the high incidence of inhibitors with ultrapurified and recombinant FVIII reported in previously untransfused patient may be borne in mind.


Value of liquid crystal contact thermography and plasma level of D-dimer for screening of deep venous thrombosis following general abdominal surgery.

Because the use of radioactive fibrinogen uptake test (FUT) has become questionable both for ethical (risk of virus transmission) and technical (lack of sensitivity) reasons, we investigated the potential value of two alternative methods for screening of asymptomatic deep venous thrombosis following elective digestive surgery: liquid crystal contact thermography (LCCT) and measurement of plasma concentration of D-dimer (DD), as compared with bilateral ascending phlebography. Out of 194 patients, 185 underwent phlebography on the 8th (0-19, median and range) postoperative day. Despite prophylaxis with low-molecular-weight heparin and elastic stockings, DVT was detected on phlebography in 58 legs of 45 patients. Sensitivity of LCCT with respect to the presence of DVT was 55% (n = 184 patients) or 28% (n = 368 legs) with a specificity of 67% and 82%, respectively. These poor performances were obtained despite a good interobserver agreement for the LCCT assessments (overall kappa coefficient of 0.66 between three experts). The most accurate cut-off of DD for discriminating patients with or without DVT was 3,000 micrograms/l, as determined by ROC curve analysis. Sensitivity of a DD level of more than 3,000 micrograms/l for the presence of phlebographically documented DVT on the 8th postoperative day was 89% for a specificity of 48%. Thus, LCCT cannot be used for screening of postoperative, mainly asymptomatic DVT following general surgery. On the other hand, measurement of plasma DD may be useful for initial screening, a negative result (level less than 3,000 micrograms/l) allowing to exclude DVT (negative predictive value of 93%) and a positive result (positive predictive value of 35%) requiring confirmation by phlebography.(ABSTRACT TRUNCATED AT 250 WORDS)


Thrombospondin levels in patients with malignancy.

Thrombospondin (TSP), a large glycoprotein present in platelets, and various normal and tumor tissues, has recently been shown to promote cell adhesion and platelet aggregation. Most importantly because TSP has been shown to promote metastasis of melanoma tumor cells to the lung in a murine model (1) and since thromboembolic events commonly occur in patients afflicted with metastatic tumors, we explored the role of TSP in human cancer by measuring TSP blood levels in patients with various malignant neoplasms. Blood TSP levels were measured by indirect enzyme-linked immunoadsorbent assay (ELISA) from 20 control subjects, 22 patients with gastrointestinal (GI) cancer, 18 patients with breast cancer, and 17 patients with lung cancer. Control subjects consisted both of healthy subjects and acutely ill patients with no malignancies. TSP levels of both healthy and acutely ill controls were found to range between 245-440 ng/ml with a mean of 365 ng/ml. In contrast, elevated levels of TSP greater than the mean value of 400 ng/ml for controls ranging between 590-3,650 ng/ml were found in 20/22 (91%) patients with GI malignancies, 13/18 (72%) patients with breast cancer, and 15/17 (88%) with lung cancer. Mean TSP levels of GI, breast, and lung cancer patients were 3, 2, and 3 fold greater than controls, respectively. Increased blood TSP levels in patients were not due to increased levels of platelets since both control and patient groups had platelet counts within the normal range. These results suggest that TSP may play a role in tumor cell metastasis in man and could serve as a blood marker for metastasis.


Tumor necrosis factor induces von Willebrand factor release in healthy humans.

Tumor necrosis factor (TNF) is an important mediator of the host responses to systemic infection. To investigate the effect of TNF on the release of von Willebrand factor (vWF) into the circulation, we performed a controlled study in six healthy men, sequentially measuring the plasma concentrations of vWF antigen after a bolus intravenous injection of recombinant human TNF (50 micrograms/m2). TNF induced a marked increase in vWF antigen plasma levels, becoming significant after 45 min and peaking after 4 h (percentage increase from base line: 351 +/- 46; p less than 0.0001, TNF versus saline). The multimeric organization of circulating vWF was not affected by TNF. We conclude that TNF may be an early mediator of increased vWF secretion in systemic infection.


Heparin binding to plasma proteins, an important mechanism for heparin resistance.

Heparin dosage requirements vary widely among patients with venous thromboembolism. In this study, we measured the proportion of anticoagulantly-active heparin which was reversibly bound and neutralized by plasma proteins (defined as reversible heparin neutralization) in the pre-treatment plasma (in vitro) and in the 6 h post-treatment plasma (ex vivo) of patients with venous thromboembolism treated with a fixed dose of heparin. Reversible heparin neutralization was assessed by comparing the heparin levels measured as anti-factor Xa activity before and after the addition of low affinity heparin which is essentially devoid of anti-factor Xa activity, in order to displace heparin bound to plasma proteins. The results indicate that reversible heparin neutralization due to binding to plasma proteins is a major determinant of the anticoagulant response to a fixed dose of standard heparin 6 h post-treatment and of the eventual heparin dose required to achieve a therapeutic anticoagulant effect on days 3-5 of heparin treatment.


A novel sensitive assay for functional factor XII based on the generation of kallikrein-C1-inhibitor complexes in factor XII-deficient plasma by glass-bound factor XII.

We developed a very sensitive assay for functional factor XII. This assay is based on the property of glass-bound factor XII to activate prekallikrein (PK) into kallikrein in factor XII-deficient plasma, which is assessed by measuring the formation of kallikrein-C1-inhibitor complexes in this plasma by radioimmunoassay. Incubation of varying amounts of factor XII in glass tubes led to a dose-dependent increase in kallikrein-C1-inhibitor complexes in factor XII-deficient plasma with a lower limit of detection of +/- 20 pg of factor XII. The specificity of the assay for factor XII was demonstrated by experiments with plasmas deficient for factor XII, PK or high molecular weight kininogen (HK) and by incubation of factor XII with Polybrene or with a monoclonal antibody that inhibits the amidolytic and procoagulant activity of factor XII. The high sensitivity of the assay appeared to be due to the inability of C1-inhibitor to inhibit factor XII bound to glass, which resulted in a molar ratio of generated kallikrein to glass-bound factor XII of at least 100:1. This assay for factor XII may be a feasible tool in studies on structural and functional aspects of (recombinant) factor XII species synthesized by cultured cells.


Beta 2-glycoprotein I deficiency and the risk of thrombosis.

beta 2-glycoprotein I (beta 2-GP I) is a plasma protein with a high affinity for negatively charged surfaces. In vitro this protein shows a variety of anticoagulant properties (inhibition of contact activation and platelet dependent prothrombinase activity). Therefore we studied the possibility that a hereditary beta 2-GP I deficiency is a risk factor for (familial) thrombophilia. Plasma beta 2-GP I levels were measured in healthy volunteers and four different groups of patients with (familial) thrombophilia. In these 5 groups the prevalence of beta 2-GP I deficiency (i.e. beta 2-GP I antigen less than 77%) was found to be very similar (6.8-12.5%) and statistically not significantly different. This observation suggests that beta 2-GP I deficiency in itself is not a risk factor for thrombosis. One thrombophilic patient was found to be homozygous deficient of beta 2-GP I. The transmission of the defect in his family followed autosomal inheritance. One of his brothers was also homozygous deficient and at the age of 35 years still free of thromboembolic complications. The possibility that beta 2-GP I deficiency could be an additional risk factor for the development of thrombophilia in families with protein C deficiency was evaluated in a panel of 70 unrelated patients with clinically dominant protein C deficiency. The prevalence of beta 2-GP I deficiency in this group of patients (12.8%) was very similar to that in other groups of normals and patients. Moreover, there was no difference in the frequency of beta 2-GP I deficiency in symptomatic and asymptomatic protein C deficient patients.