Short-term treatment of Paget's disease of bone with ipriflavone.

Ipriflavone (IP), an isoflavone derivative, seems to prevent the loss of bone mass through the inhibition of bone resorption, mainly inhibiting the recruitment of osteoclasts. We investigated whether a brief course of treatment with IP can reduce biochemical parameters of accelerated bone turnover and bone pain in patients with active Paget's disease of bone. Sixteen patients (9 males and 7 females) with active Paget's disease were randomly allocated to two different crossed-over dose regimens of treatment with IP (600 mg/day vs. 1200 mg/day). Each treatment course lasted 30 days and the wash-out period between the two sequences was 15 days. Serum alkaline phosphatase (Al.Ph.) and urinary hydroxyproline/creatinine excretion (HOP/Cr) were reduced after each sequence. At the end of the 600/1200 mg/day treatment sequence, serum Al.Ph. and HOP/Cr decreased with 32% and 25.6% respectively. At the end of the 1200/600 mg/day treatment sequence, serum Al.Ph. and HOP/Cr decreased with 33% (P < 0.01) and 24.1% (P < 0.05) respectively. Furthermore, a significant decrease in bone pain was observed during the 1200/600 mg/day sequence (P < 0.01). Both treatment schedules were well tolerated and the patients' compliance resulted excellent. Our results indicate that short-term treatment with IP can reduce biochemical parameters of disease activity and bone pain in patients with active Paget's disease of bone.


Effects of ipriflavone on bone mass and calcium metabolism in postmenopausal osteoporosis.

Recently it has been demonstrated that ipriflavone (IP), an isoflavone derivative, is able to increase bone mass in patients with established postmenopausal osteoporosis (PMO). Here we present a preliminary report of a 2-year multicenter, double-blind, placebo-controlled clinical study performed in order to evaluate the efficacy and tolerability of IP in PMO. A large number of patients with PMO, referred to 12 Italian centers, was randomly divided into 2 groups and treated with oral IP (600 mg/day) or placebo (Pl). All patients received an oral Ca supplement (1 g/day). One hundred and twenty six patients completed 1 year of the study. Bone mineral density (BMD) of the distal radius, measured by DPA, serum osteocalcin (BGP), and urinary hydroxyproline excretion (HOP/Cr), were measured before and after 12 months. After 12 months, a significant increase in BMD was observed in the IP-treated group (P < 0.05). IP determined a reduction of HOP/Cr, while in Pl-treated patients a significant increase of this index, as well as of BGP, was observed. After 12 months the difference between the two groups resulted significant (P < 0.05) for BGP. The drug was well tolerated and the patients' compliance to the oral treatment resulted excellent. The results of this study indicate that IP is able to increase bone mass in patients with PMO.


Ipriflavone and low doses of estrogens in the prevention of bone mineral loss in climacterium.

Estrogen replacement therapy can counteract all postmenopausal symptoms. While low estrogen doses (0.15-0.30 mg of conjugated estrogens/day) can counteract neurovegetative and psychological symptoms, higher estrogen doses (at least 0.625 mg of conjugated estrogens/day) are required to prevent bone mineral loss in postmenopausal women. However, if contra-indications to high estrogen doses exist, drugs other than estrogens can represent a suitable treatment for postmenopausal osteoporosis both alone or in combination with low estrogen doses. Experimental and clinical data have shown that ipriflavone is effective in the treatment of established postmenopausal osteoporosis. With the purpose of evaluating whether ipriflavone is able to enhance estrogen activity on bone metabolism, 133 postmenopausal women were randomly submitted to the treatment with: (1) placebo; (2) 0.15 mg/day of conjugated estrogens; (3) 0.30 mg/day of conjugated estrogens; (4) 0.15 mg/day of conjugated estrogens plus 600 mg/day of ipriflavone; (5) 0.30 mg/day of conjugated estrogens plus 600 mg/day of ipriflavone. One g/day of calcium supplementation was given to all women. In all subjects bone mineral density was measured before and after 6 and 12 months of treatment at the distal radius by dual-photon absorptiometry. A moderate decrease of bone mineral density was evidenced in women submitted to placebo or to estrogen therapy alone. By contrast, an increase of BMD was measured after 12 months of treatment in the women treated with 0.15 (not significant) or 0.30 mg/day (P < 0.01) of conjugated estrogens associated with ipriflavone. Both dosages of conjugated estrogens were able to induce a significant reduction of neurovegetative symptoms. The increase of bone density obtained with the combination of conjugated estrogens with ipriflavone demonstrates that this combination improves the effects of low estrogen doses on bone mass representing a satisfactory approach in the prevention and treatment of all symptoms related to the climacteric syndrome.


Effect of ipriflavone on bone mass in elderly osteoporotic women.

A study in elderly osteoporotic women was performed to assess the effect of one year treatment with ipriflavone (IP) on bone mass and bone biomarkers. Twenty-eight women aged over 65, with diagnosis of osteoporosis and X-ray evidence of at least one vertebral fracture, were treated with IP tablets (600 mg/day) or placebo (PL), according to a randomized, double-blind, parallel-group design. One g/day calcium supplementation was given to all patients. After 12 months a significant increase (+6%, P < 0.05) of bone mineral density (BMD) at the distal radius (DPA) was obtained in the IP-group. Serum osteocalcin (BGP) and urinary HO-proline/creatinine (HOP/Cr) values were reduced in the same group. BMD values did not change (-0.3%) in the placebo group. One woman of the PL-group was withdrawn from treatment because of worsening of pain, due to new vertebral crushes. Side effects (mainly gastrointestinal) arose in 8 IP- and in 5 PL-treated women. The compliance to the oral administration was good.


Preliminary analysis of the care of injured patients in 33 British hospitals: first report of the United Kingdom major trauma outcome study.

To measure the effectiveness of management of major trauma in the United Kingdom. Review of the care of all seriously injured patients seen over two years. 33 hospitals which receive patients who have sustained major trauma. 14,648 injured patients admitted for more than three days, transferred or admitted into an intensive care bed, or dying from their injuries. Death or survival in hospital within three months of the injury. 21% of seriously injured patients (1299) took longer than one hour to reach hospital. Time before arrival at hospital was not related to severity of injury. A senior house officer was in charge of initial hospital resuscitation in 57% (826/1445) of patients with an injury severity score > or = 16. More senior staff were commonly responsible for definitive operations, but only 46% (165/355) of patients judged to require early operation arrived in theatre within two hours. Mortality for 6111 patients sustaining blunt trauma and treated in the 14 busiest hospitals was significantly higher (actual 408, predicted 295.6, p < 0.001) than in a comparable North American dataset. Large differences in the 14 hospitals assessed could not be explained by variations in case load or facilities. In contrast, the outcome of the 4.1% (597) of patients with penetrating injuries was better than that of a comparable group in the United States. Analysis of the 415 penetrating injuries with complete data showed that 15 patients died (19.3 predicted; p = 0.04). The initial management of major trauma in the United Kingdom remains unsatisfactory. There are delays in providing experienced staff and timely operations. Mortality varies inexplicably between hospitals and, for blunt trauma, is generally higher than in the United States.


Severity of imported falciparum malaria: effect of taking antimalarial prophylaxis.

To investigate the effects of antimalarial chemoprophylaxis and other variables on the severity of falciparum malaria. Review of consecutive malaria cases between 1987 and 1991. The Hospital for Tropical Diseases, London. 250 consecutive cases of mild and 51 consecutive cases of severe falciparum malaria. Prophylaxis was taken in 52.4% (131/250) of the cases of mild malaria and 21.6% (11/51) of cases of severe malaria. Severe malaria was more common in white patients than in those of African origin and was also seen more commonly in people returning from central, southern, and east Africa than in those returning from west Africa. Patients with severe malaria presented sooner than patients with mild malaria. Prior chemoprophylaxis led to a reduction in the severity of falciparum malaria. Ethnic origin, time to presentation, and sex were also associated with the severity of malaria.


Cost of urology: financial audit in a clinical department.

To cost a clinical unit over one month in 1991, to cost treatment of individual patients from audit data, and to compare this costing method with the hospital charging system. A financial breakdown was obtained for one month's work. Ward stay, operating time, investigations, and outpatient visits were costed and a formula (episode = days on ward+hours of operating+investigations+outpatient visits) was used to cost patient episodes from audit data. The adult urology unit in a teaching hospital. Costs for each part of patients' treatment. Total cost was 147,796 pounds for 159 admissions, 738 inpatient days, 131 operations in 29 operating lists, and 615 outpatient visits. An uncomplicated transurethral prostatectomy cost 1140 pounds but complications increased this to 1500 pounds in another patient. The costs of diagnostic cystoscopy were 130 pounds in outpatients, 240 pounds in day surgery, and 430 pounds in inpatients. Hospital charges do not reflect the individual costs of treatment, charges being greater than costs for some patients and lower than costs for others. Clinicians can produce a financial analysis of their work and cost their patients' treatment. Audit is strongly advocated as a resource planning tool.


Outcome of breech delivery at term.

To compare neonatal mortality and morbidity in term infants presenting by the breech and delivered vaginally or by caesarean section. Population based comparison of outcomes. Data derived from the St Mary's maternity information system. North West Thames Regional Health Authority, 1988-90. 3447 singleton fetuses presenting by the breech at term. Intrapartum and neonatal mortality, low Apgar scores, intubation at birth, and admission to special care baby units. After the exclusion of babies with congenital anomalies the incidence of intrapartum and neonatal death associated with vaginal birth was 8/961 (0.83%) compared with 1/2486 (0.03%) in babies born by caesarean section (relative risk 20, 95% confidence interval 2.5 to 163). The numbers of low Apgar scores and neonatal intubation were doubled in babies born vaginally or by emergency caesarean section compared with those delivered by elective operation. The good neonatal outcome associated with elective caesarean delivery of the term breech fetus may influence the decision of women and their obstetricians about mode of delivery.


Can secular trends in child growth be estimated from a single cross sectional survey?

To formulate and evaluate a new method to measure secular trends in child growth based on the cross sectional collection of heights of children and young adults. Trends in child growth obtained from comparison of two national surveys made with an interval of 15 years were compared with estimates obtained from comparison of height deficits of children and young adults in the more recent survey. Brazil. Random sample of children (6 and 7 years old) and young adults (21 and 22 years old) living in Brazil in 1974 and 1989 (a total of 23,271 subjects in 1974 and 5479 in 1989). Increments in average heights of 6 and 7 year old children in a 15 year period. Mean height of 6 year old children increased 4.0 cm (boys) and 3.3 cm (girls) from 1974 to 1989. Similar results were obtained by subtracting, in the 1989 survey, mean height deficits found at ages 21 and 6 (3.8 cm for males and 3.5 cm for females). Positive changes in the mean height of 7 year old children could also be predicted by subtracting, in the 1989 survey, height deficits found at ages 7 and 22. Findings of this study support the hypothesis that secular trends in child growth can be estimated by comparing height deficits observed in children and young adults.


Effect of maintenance chemotherapy in childhood on numbers of melanocytic naevi.

(a) To determine whether children given chemotherapy for haematological malignancy have significantly more melanocytic naevi than age matched children in the local population; (b) to establish whether any observed variation in naevus counts from normal is seen at the start of maintenance chemotherapy. Follow up of 29 consecutive children starting maintenance chemotherapy, with parental interview and count of all melanocytic naevi > or = 2 mm on the child's skin. Assessment repeated three years later after completion of maintenance chemotherapy. Other dermatological problems identified at either visit were also recorded. Royal Hospital for Sick Children, Glasgow. At the start of maintenance chemotherapy all children had total body counts of melanocytic naevi within the normal range established for age matched children in the local population. Three years later total body naevus counts were significantly increased, the median increase being 66 naevi per child (95% confidence interval 57 to 94). The only other problem noted in these children was relatively poor regrowth of scalp hair. Children on maintenance chemotherapy for haematological malignancies develop an excessive number of melanocytic naevi. Excessive numbers of melanocytic naevi are the most important risk factor for melanoma in the general population. These children should have periodic skin examinations at their follow up visits, and both child and parent should be educated about clinical features of early melanoma.


Female streetworking prostitution and HIV infection in Glasgow.

To identify the extent of HIV infection and injecting drug use among female streetworking prostitutes in Glasgow; to estimate the size of the female streetworking prostitute population in the city; and to estimate the number of HIV positive women working as prostitutes on the streets in Glasgow. Observation and interviewing of female prostitutes over seven months in red light district; analysis of saliva samples for presence of antibodies to HIV; capture-recapture approach to estimating the size of the female streetworking prostitute population. Glasgow. 206 female streetworking prostitutes. Number of women with antibodies to HIV, self reported use of injecting drugs, history of contact with 206 women. Saliva samples were requested from 197 women; 159 (81%) provided samples. Four (2.5%, 95% confidence interval 0.7%-6.3%) of the samples were positive for HIV, all of which had been provided by women who injected drugs. Of the 206 streetworking women contacted 147 (71%) were injecting drug users. About 1150 women are estimated to work on the streets in Glasgow over a 12 month period. HIV is not as widespread among female prostitutes as many reports in the tabloid press suggest. A greater proportion of female streetworking prostitutes in Glasgow are injecting drugs than has been reported for other British cities.


Risk of prostate, ovarian, and endometrial cancer among relatives of women with breast cancer.

To investigate the risk of prostate, ovarian, and endometrial cancer among relatives of patients with breast cancer. Cohort study of 947 pedigrees in which the proband had breast cancer, linked with the Icelandic cancer registry. Iceland. The 947 pedigrees included 29,725 people, of whom 1539 had breast cancer, 467 had prostate cancer, 135 ovarian cancer, and 105 endometrial cancer. Risk of prostate, ovarian, and endometrial cancer among blood relatives of women with breast cancer compared with risk in spouses. The risk of prostate cancer was significantly raised for all relatives (1.5), first degree relatives (1.4), and second degree relatives (1.3) of women with breast cancer. Risk of ovarian cancer was raised for all relatives (1.9) and first degree relatives (1.9) and risk of endometrial cancer was raised for all relatives only (1.9). The risk of prostate cancer was raised if the proband with breast cancer had a first degree relative with prostate cancer. Coaggregation exists between breast cancer and cancers of the prostate, ovaries, and endometrium. This risk relation is probably based on genes which act by increasing the risk for cancer at these sites. Environmental factors that are common among relatives may also play a part. Continued research is required into pathophysiological mechanisms that could explain these observations.


Cost implications of the British Pacing and Electrophysiology Group's recommendations for pacing.

To compare present pacing practice with the recommendations recently published by the British Pacing and Electrophysiology Group and to assess the increase in annual budget required to implement these recommendations in a regional cardiothoracic unit. Retrospective analysis of pacemaker implantation for 1991 with calculation of the costs required to implement the group's recommendations based on average 1991 costs of the types of pacing generators and electrode leads used. Regional cardiothoracic unit for South West Thames Health Authority. 433 consecutive patients receiving permanent pacemaker generators: 76 (18%) with sinus node disease; 270 (62%) with atrioventricular block; 25 (6%) with both sinus node disease and atrioventricular block; 59 (14%) with chronic atrial fibrillation and atrioventricular block; and 3 (1%) with carotid sinus or malignant vasovagal syndromes. Only 102 (24%) patients received pacemaker generators recommended by the British Pacing and Electrophysiology Group; however, 355 (82%) patients were older than 65 years, and 264 (61%) were aged 75 or over. The cost of hardware for pacing was 462,885 pounds. Using generators as recommended would have cost 810,525 pounds for "optimal" systems (an increase of 75%) and 710,750 pounds for "alternative" systems (an increase of 54%). These increases would have been considerably reduced by limiting the use of sophisticated pacing to younger patients (aged under 75). Further savings could be made by using the least expensive pacing models available. Implementing these recommendations should reduce morbidity related to bradyarrhythmia but will lead to major increases in pacing costs. Age and patients' expected activity may be used to select simple pacing systems and thus to contain cost. More research is needed to determine which patient groups will benefit most from complex pacing systems.


The role of non-steroidal anti-inflammatory drugs in acute liver injury.

To investigate the association between use of non-steroidal anti-inflammatory drugs and serious, acute non-infectious liver injury. Retrospective cohort study, cross over design. Health records from provincial database in Saskatchewan, Canada, 1982-6. 228,392 adults who contributed 645,456 person years. All were either using or had used non-steroidal anti-inflammatory drugs. Number and type of prescriptions for non-steroidal anti-inflammatory drugs. Admission to hospital for newly diagnosed acute liver injury. There were 34 admissions to hospital; 16 among subjects currently using non-steroidal anti-inflammatory drugs and 18 among subjects who were not. The incidence rate among current users was 9 per 100,000 person years (95% confidence interval 6 to 15 per 100,000 person years). Subjects currently using non-steroidal anti-inflammatory drugs had twice the risk of newly diagnosed liver injury as those not currently taking these drugs (rate ratio 2.3; 95% confidence interval 1.1 to 4.9) and an excess risk of 5 per 100,000 person years. The age and sex adjusted risk ratio was 1.7 (0.8 to 3.7). The strength of the association increased when only cases with no concomitant use of other hepatotoxic drugs were considered (4.0; 0.9 to 19.0). The rate ratio for people having received one to nine prescriptions was constant. There was no increased risk with long duration of treatment (1.0; 0.3 to 3.5). There is a small excess risk of serious, acute non-infectious liver injury associated with the use of non-steroidal anti-inflammatory drugs.


Lifestyle advice in general practice: rates recalled by patients.

To document how often patients with varying cardiovascular risk levels reported receiving lifestyle advice from general practice. Cross sectional descriptive survey by postal questionnaire. 5 general practices in Bedfordshire. 4941 people aged 35-64 years who had consulted a general practitioner at least once during the 12 months before completing the questionnaire and who subsequently attended for a health check as part of the OXCHECK trial. Report of having received advice from a general practitioner or practice nurse about smoking, alcohol consumption, exercise, or diet during the 12 months before completing the questionnaire. Cardiovascular risk assessed by a nurse during structured health check. The overall reported rate of advice was 27% for smoking, 4.5% for exercise, 12% for diet, and 3% for alcohol consumption. Those with unhealthy behaviour profile or at increased cardiovascular risk received more advice--for example, 47% of smokers with a history of cardiovascular disease received advice on smoking. Among those at increased risk, men were more likely than women to receive advice about exercise (11% v 4%, p = 0.04) and alcohol consumption (10% v 4%, p = 0.007), while women received more advice about weight (17% v 23%, p < 0.001). The rate of receiving advice was unaffected by age, marital status, or social class. The low rate of lifestyle advice reported by patients implies that more preventive advice could be provided in primary care.


Intermetatarsal synostosis after treatment with Ilizarov apparatus: a case report.

A transmetatarsal pin was used as part of an Ilizarov apparatus to correct equinovarus deformity of a foot in a 7-year-old patient. The pin created synostosis between the metatarsal bones. The synostosis led to persistent flattening of the transverse arch of the foot, producing a painful gait. To avoid this problem, we recommend that the metatarsal wire be placed only through the first and fifth metatarsals rather than through the neighboring metatarsals.


Humeral lengthening and bone transport using the Ilizarov technique.

The authors present their results of Ilizarov treatment of eight humeral length deficits and bone defects in seven consecutive patients treated at the Hospital for Joint Diseases. The mean humeral lengthening achieved was 9.8 cm. The lengthening goal was completely achieved in six cases, while two cases achieved over 80% of the desired length. No permanent neurovascular or infectious complication occurred. The authors suggest that the Ilizarov technique is a viable method in treating severe humeral length deficits or bone defects.


Noninvasive vascular monitoring during limb lengthening.

Transcutaneous wires and pins in wire-tension Ilizarov external fixators provide frame stability, transfix and transport bone segments, produce distraction, and stimulate transosseous osteogenesis. Vascular compromise by the transfixing pins and wires is nevertheless an ongoing possibility. Based on earlier studies of a two-phase method of measuring vascular blood blow, noninvasive vascular monitoring was performed on three patients undergoing Ilizarov method limb lengthening.


Pin care using the Ilizarov apparatus: recommended treatment plan in Kurgan, Russia.

Differences in the care of the pins used in association with the Ilizarov apparatus and technique are found in various countries and institutions. During a recent visit to the Ilizarov Institute in Russia, the methods of caring for the Ilizarov pins were extensively investigated and documented. The U.S. infection rate at pin sites has been reported to be nearly 10%. No specific infection rate has been reported from Russia. What constitutes an infection at the Ilizarov Center in Kurgan was investigated, as were methods of treatment. Our conclusion is that pin care in Russia is conducted under a more vigorous and stringent regimen, but less often, than in the United States. Soviet record keeping is different, and therefore the infection rates cannot be compared. In Kurgan, specific diligence is exercised in addressing the problems at each pin site. Treatment is directed toward alleviating these problems.


Rigidity of half-pins for the Ilizarov external fixator.

The success of the Ilizarov technique is due to the combination of the biomechanics of its external fixator and the biology of distraction osteogenesis. The stability and stiffness of the conventional Ilizarov fixator is attributed to its use of a K-wire cross structure. The disadvantages of this structure include pain, and possible neurologic and vascular injuries when the wires are introduced into crucial neurovascular areas, as well as increased frame complexity and construction. Reducing the number of wires decreases these problems, but also decreases the stiffness of the system. Hybrid (wire and half-pins) Ilizarov fixators and half-pin fixators are also being used in an attempt to alleviate these problems. Half-pins have been described by Fleming et al. and Green as causing minimal transfixation of the surrounding soft tissues and capable of and being inserted into anatomically safe areas. The stiffnesses of the hybrid systems have not been measured. This study reports on the stiffness of different wire and half-pin systems that were biomechanically tested in axial loading, anterior-posterior bending, medial-lateral bending, and torsional loading. The results demonstrated that the conventional Ilizarov fixator with wires possesses a high axial stiffness, whereas the fixator with half-pins possesses higher stiffness under bending and torsional loads. To obtain adequate stability, the use of hybrid Ilizarov frames with one wire and two or more half-pins (5 or 6 mm in diameter), or larger half-pin frames (5 or 6 mm) with three pins is recommended.


The theoretical application of inclined hinges with the Ilizarov external fixator for simultaneous angulation and rotation correction.

The mathematical concepts of single-cut osteotomies for simultaneous correction of angulation and rotation have been adapted and simplified for gradual distraction-osteogenic correction with the Ilizarov external fixator. Validation studies were performed analytically, using a solid modeling analysis, and experimentally with an Ilizarov external fixator mounted on a wood dowel. The resultant equations have been simplified and are easy to use. Starting from the hinge which would correct the angulation, the axis must be reoriented in the horizontal plane by half the rotation deformity (R/2) and given an inclination slope equal to the rotation divided by the angulation (R/A).


Control of interfragmentary micromotion in Ilizarov distractional osteogenesis.

Growth of the regenerate is affected by various factors during the course of Ilizarov distractional osteogenesis. One of the chief biomechanical factors that influences the quality and rate of bone formation is fixator stiffness. A four-ring Ilizarov apparatus was configured around a synthetic tibia. In a series of trials involving a uniform axial load, different transfixing wire tensions, and the separation of paired proximal and distal rings, fragment displacement was measured. Preliminary results suggest that the effect produced by the distraction of ring pairs on interfragmentary micromotion is as significant as pretensioning of the wires.


Pelvic support femoral reconstruction using the method of Ilizarov: a case report.

A 15-year-old boy presented with a fixed, irreducible congenital dislocation of the hip associated with other multiple lower extremity growth disturbances secondary to neonatal multifocal osteomyelitis. The affected hip had very limited abduction, and the patient had a very severe Trendelenburg gait secondary to the dislocation. The hip was reconstructed according to the Ilizarov method, by a combination of maximum proximal femoral adduction osteotomy in the subtrochanteric region and distal femoral corticotomy, to permit the gradual realignment of the knee into the new weight-bearing axis produced by the proximal osteotomy. Total fixation time for the femoral reconstruction was two months. Five months after removal of the apparatus, the patient was returned to full function with a remarkably improved gait.


[The effect of digoxin on the cerebral blood flow in rabbits].

Hydrogen clearance was used in chronic experiments on 10 unrestrained rabbits to study the influence of digoxin (0.1 mg/kg, i. v.) on the time course of changes in the local brain circulation in the sensorimotor, temporal and optic cortex. It has been revealed that digoxin is capable of exerting varying influence on circulation in the above-mentioned regions. Potential mechanisms of the data obtained are under discussion.


[Calcium and calcium-channel blockers in the healing of an experimental myocardial infarct].

It has been shown in experiments on 36 dogs with experimental myocardial infarction (MI) that the effect of calcium and blockers of calcium channels largely depends on the initial condition of reactivity and is realized via changes in lipid peroxidation (LPO). In MI, calcium enhances necrotic processes whereby aggravating disorders in its healing in case of high reactivity and returns them to normal, thus contributing to optimization of its healing in animals with low reactivity. Calcium channels blockers attenuate necrotic processes associated with MI and lead to its better healing in the presence of high reactivity and aggravate disorders in its healing in animals with low reactivity. Consideration of the body reactivity, the differentiated use of calcium drugs and calcium channels blockers should be regarded as an effective approach to optimization of the healing of complicated forms of MI.


[The effect of the antioxidant ionol as a liposome component on the function of the isolated and ischemic heart].

The anti-ischemic and toxic effects of different doses of the antioxidant ionol (butyl hydroxytoluene, BHT) introduced into the Krebs-Henseleit medium composed of monolayer liposomes of egg phospholipids before or 30 minutes after total ischemia of the heart were studied on a model of perfusion of isolated Wistar rat heart by the method of Langendorff-Fallen. It has been demonstrated that ionol, after its addition to the perfusate in the preischemic period, exerts an anti-ischemic effect in concentrations of 10(-6), 3 x 10(-6) and 10(-5) M; in the postischemic period, in concentrations of 3 x 10(-6) and 10(-5); the protective effect of ionol in the postischemic period is less pronounced. In higher doses (3 x 10(-5) and 10(-4) M) ionol produces a toxic action which is more remarkable and is less reversible in respect to the ischemized than to the nonischemized heart, and is realized rather through the dysfunction of heart muscle relaxation. The conclusion is drawn that there is a possibility of using ionol in doses of 10(-6) to 10(-5) M as a constituent of liposomes for addition to perfusion, conservant and cardioplegic solutions as an anti-ischemic remedy.


[The effect of a new drug form for the intravenous administration of vitamin K1 on the blood coagulation system].

In rabbits with experimental hypocoagulation induced by phenylin, the use of a new dosage form of vitamin K1 for intravenous injections in does of 1 and 5 mg/kg led, in contrast to vicasol in a dose of 0.4 mg/kg, to an increase of the prothrombin index after 2 hours and to its complete normalization after 4 hours. Intravenous injection of vitamin K1 into intact animals did not entail any changes in the activated partial thromboplastin time, thrombin and prothrombin time, in the content of fibrinogen and products of its biotransformation, antithrombin III activity, and fibrinolytic activity or in the count of platelets and their aggregation capacity.


[The effect of the surface-active substance proxanol on the ischemic myocardium].

The anti-ischemic effect of a 4% proxanol solution (intravenous injection in a dose of 10 ml/kg 60 min after occlusion) was compared with that of a salt solution in experimental acute ischemia of dog myocardium, induced by partial occlusion of the anterior descending branch of the left coronary artery. Overall estimation of the effect of SAS infusion has demonstrated that this drug has a beneficial effect on hemorheology (decreases blood viscosity and vascular resistance, increases coronary blood flow), stabilizes oxygen supply of the myocardium and lowers the extent of its ischemia-induced damage (eliminates ST segment depression). However, the cardiodepressive action of proxanol does not allow for compensation of the ischemia-induced decrease in myocardial contractility and pump function of the heart.


[The effect of dibunol on lipid peroxidation and the alpha-tocopherol level in the lungs of rats with acute blood loss].

Experiments on linear male rats were made to study the pathophysiological mechanism of the synthetic antioxidant dibunol on the levels of primary and end products of lipid peroxidation (LPO) and of alpha-tocopherol (TP) in the lungs in acute hemorrhage. Dibunol in a dose of 120 mg/kg injected 5 min after the hemorrhage inhibited LPO to the level in intact animals and raised the content of TP to the level seen in operated animals without any hemorrhage. The conclusion is drawn about a possibility of using dibunol for correction of disturbed pulmonary metabolism in urgent conditions associated with blood loss.


[The effect of solubilized alpha-tocopherol acetate on resistance to experimental physical loading].

A single intravenous injection of solubilized alpha-tocopherol acetate to Wistar male rats in doses of 25, 50 and 100 mg/kg noticeably increased the animals' working capacity. The stimulation effect appeared 18 hours after the injection and was observable for two weeks. Utilization of glucose reserves in bioenergy supply of muscle activity has been shown. The maintenance of the action for such a long time may be accounted for by high metabolic stability of solubilized alpha-tocopherol acetate.


[The interaction of the Ca2(+)-channel blocker verapamil with cardiac glycosides in the rat kidney].

Strophanthine (0.1 mg/kg, i. v.) and digoxin (0.1 mg/kg, i. v.) increase blood supply of the cortex and medullary layer of the kidneys of anesthetized rats and significantly raise excretion of water and sodium by the kidneys. Verapamil, a blocker of Ca(2+)-channels (0.25 mg/kg, i. v.) attenuates the increment of the blood flow in the internal zone of the cortex and external zone of the medullary layer but does not prevent the rise of diuresis and excretion of sodium with urine under the action of the above-indicated drugs. The conclusion is drawn that realization of the vasodilatory effect of cardiac glycosides in the kidneys is partially connected with a lowering of the content of Ca2+ in myofibrils whereas formation of their tubular effect does not depend on the changes in Ca2+ concentration in nephron cells.


[The mechanism of action of dimephosphon].

It has been established in experiments on rats that the 7-day administration of dimephosphon per os increases blood levels of total mercapto groups and glutathione, changing the correlation of its forms in favour of the oxidized ones. This course of dimephosphon administration reduces blood concentration of lipid peroxidation products. The significance of these mechanisms in realization of the pharmacological effects of dimephosphon is under discussion.


[The comparative action of isoniazid, rifampicin and ethambutol on liver function].

It has been established in experiments on white rats that antituberculous drugs (isoniazid, rifampicin, ethambutol) given in toxic doses affect the liver, its membranes and organelles, inhibit bile production and bioenergy. This is supported by activation of aspartate and alanine aminotransferases, (ALT and AST), alkaline phosphatase in blood serum and acid phosphatase in the liver, by a decrease of the activity of Na(+)-, K(+)-ATPase, succinate dehydrogenase and cytochromoxidase in the liver, lowering of the rate of bile secretion, excretion of bile acids, bilirubin and cholesterol with bile. Provided the drugs are administered in combination, the hepatotoxicity rises, particularly in combination of isoniazid with rifampicin, and especially as isoniazid is combined with rifampicin and ethambutol.


[The antioxidant activity of bis-quaternary ammonium compounds of the methylene series].

Experiments on albino rats were made to reveal antioxidant activity of bisquaternary ammonium compounds of the methylene series (ethonium, thionium and dodeconium). It is determined by the enhancement of superoxide anion radicals neutralization and splitting of lipoperoxides.


[The correction of disorders in the pharmacodynamics of drugs metabolized in the liver in the postnatal ontogeny of rats with acute hepatitis].

It has been established in experiments on 30 day albino rats that in acute hepatitis, the pharmacodynamics of the test drugs hexenal, amidopyrine and ethylmorphine metabolized in the liver is considerably potentiated. In contrast to silibor, phytin and zixorine, experimental therapy with benzonal brings about a complete recovery of the pharmacodynamics of the drugs under study. It is believed that benzonal holds promise in pediatrics as a remedy that restores the detoxifying potency of the liver.


[The effect of ketoconazole on the cholesterol content of the blood serum lipoproteins and bile in experimental hypercholesterolemia].

Inclusion of ketonazole (in a daily dose of 400 mg/kg for 8 days) into the diet of intact and cholesterol-fed (5% dietary cholesterol) rats produced a respective 20- and 30-percent lowering of cholesterol content in blood serum. In all the animals, the hypocholesterolemic effect of ketoconazole was realized via a decrease of the concentration of very low and low density lipoproteins. Ketoconazole also gave rise to a reduction of the concentration of cholesterol and bile acids in bile of the intact rats and of cholesterol in bile of the cholesterol-fed animals.


Multiple cytogenetic aberrations in squamous cell carcinomas of the head and neck.

Chromosomal abnormalities in short term cultures have been investigated in 10 squamous cell carcinomas of the head and neck. Of these tumours, three demonstrated clonal chromosomal abnormalities, two showed random abnormalities and 5 patients' tumours had normal karyotypes. The 5 patients with aberrant karyotypes were all from previously treated tumours, of these, 4 patients had received radiotherapy and 1 surgery. On analysis of the three clonal tumours, two were found to be polyclonal, each with five separate clones. 116 breakpoints were demonstrated from the clonal data of these tumours, and all of the chromosomes were involved, apart from number 18. In this study we found three or more breakpoints at sites 1p36, 9q32 and 11q23. 1 of the patients investigated showed a clonal abnormality involving a breakpoint at the 11q13 site, with a further 2 patients having breakpoints at 1p22--sites previously reported to have marked clustering of cytogenetic abnormalities in oral cancer patients. Only further studies will demonstrate whether the breakpoints found are of clinical significance.


[The effect of antioxidants on the fast burst of Fe2(+)-induced chemiluminescence].

A new micromethod for measuring the intensity of free radical oxidation reactions, based on an analysis of "fast flash" of iron-induced chemiluminescence parameters has been designed. The optimal concentration parameters of the reaction system have been determined. The effects of the antioxidants mexidol, probucol sodium dibunat and fenoxan have been examined in vitro.


[The cytogenetic effects of antitumor preparations with different mechanisms of action].

The cytogenetic effects of antitumor drugs with different action mechanism on the genetic structure of bone marrow hemopoietic cells were studied in experiments on CBA mice. It has been shown that single injections of doxorubicin (6 mg/kg), vinblastin (2.2 mg/kg), cyclophosphamide (250 mg/kg) and continuous administration of doxorubicin (0.95 mg/kg), vinblastin (0.24 mg/kg), cyclophosphamide (27 mg/kg) in 1/10 LD50 x 10 induce the formation of bone marrow cells with cytogenetic damage and peripheral red blood cells with micronuclei. The cytogenetic damage of hemopoietic tissue may be detectable 1-3 months after cytostatic influence.


Referral patterns of patients with oral squamous cell carcinoma, Australia.

Early diagnosis is an important factor affecting the prognosis of patients with oral cancer. Delays in diagnosis have been variously reported as being linked to the patient, the clinician or both. The purpose of this study was to investigate the referral patterns of patients with oral cancer by medical and dental practitioners, in order to assess the delays in diagnosis and to establish the reasons for these delays. 51 consecutive patients diagnosed with oral mucous membrane squamous cell carcinoma were retrospectively reviewed. In this study it was found that over one-third of the patients (38%) delayed seeking professional advice for more than 3 months after first being aware of the lesion. Initial delays in diagnosis of oral cancer was identified in one-third of the cases (17 patients), with antimicrobial medications prescribed and denture adjustments constituting the most frequently administered inappropriate therapy. General medical practitioners were more likely to encounter and refer patients with more advanced (T4) primary oral cancers than their dental colleagues. The findings of this study raise the concern that lack of patient awareness and inappropriate clinical management prevails in a community that should be better informed.


[The role of endogenous K+ in realizing the protective action of M-cholinolytics in chlorophos poisoning].

The protective effect of M-cholinolytics during the poisoning of mice with chlorophos or exogenous acetylcholine is characterized by certain specific features. An attempt to reproduce the cholinolytic effect during poisoning by organophosphorus compounds was successful in case where the intoxication by a direct cholinomimetic was carried out in the presence of KCl solution or where the animals' poisoning was preceded by administration of voltage-dependent K+ channel blockers. The conclusion is made that the increased concentration of extracellular K+ occurring as the result of poisoning with organophosphorus compounds may play a role in the mechanism of the protective action of M-cholinolytics in chlorophos poisoning.


Nass use, cigarette smoking, alcohol consumption and risk of oral and oesophageal precancer.

In a cross sectional study, conducted in Uzbekistan, an area with a high incidence of oral and oesophageal cancer, 1569 men were interviewed regarding use of nass quid, cigarette smoking and alcohol drinking. All subjects in the study had an oral examination, and oesophagoscopy was performed in 1344 men. Nass use and cigarette smoking emerged as independent risk factors for oral leukoplakia. The prevalence odds ratio (OR) for life-time nass intake equivalent rose from 1.0 in never-users to 5.17 [95% confidence interval (CI), 3.10-8.61] in the highest category; for total pack-years of cigarettes smoked the risk rose from 1.0 in never-smokers to 10.03 (95% CI, 4.9-20.6) in the highest category. There was a significant trend in risk (P < 0.001), for both factors. In the group with oral leukoplakia, the effect of nass use and cigarette smoking appeared to be additive. Cigarette smoking was also found to be an independent risk factor for oesophageal lesions and was significantly associated with chronic oesophagitis. The risk of chronic oesophagitis in the group with the highest pack-years of cigarettes smoked was approximately double that among non-smokers [Odds ratio (OR) = 2.47; 95% CI 1.34-4.56]. There was a weak association between nass use and oesophageal pathology: the highest life-time intake equivalent was associated with an OR of 1.56 (95% CI 1.09-2.23). Alcohol intake was not found to be independently associated with the presence of oral and oesophageal precancerous lesions.


[The pharmacokinetics and pharmacodynamics of pentoxifylline (trental) in the third pregnancy trimester].

As a result of studies into the pharmacokinetics of pentoxyfillin, no significant differences were established in the magnitudes of its non-model parameters in normal pregnancy and chronic placental insufficiency. However, there were differences in the metabolite formation rate in the groups under study. Distinctions were detected in the antiaggregation effect of pentoxyfillin. They consisted in a slower recovery of platelet aggregation parameters to the initial values in the first group examined. There was no good agreement between the concentrations of pentoxyfillin, its major pharmacologically active metabolite in blood plasma of pregnant women and the antiaggregation effect, which reaffirms the indirect action of this drug on platelets.


[An electromyographic method for determining the antihypoxic activity of preparations].

To measure drug antihypoxic activity, an electromyographic method was worked out. The main idea of the method is to estimate the influence of these substances on the amplitude of slow electric waves of smooth muscles on an isolated strip of rat small intestine in situ. This parameter whose value directly depends on tissue pO2 was recorded under the conditions of artificial ischemia of the intestinal strip. Circulatory hypoxia was simulated by the clamping of mesentery vessels, and the time was determined, during which the amplitude of slow electric waves reduced to 1/3 of the initial value in control animals and rats treated beforehand with the drugs under study. Antihypoxic activity of the drugs was calculated as difference in these time intervals between experiment and control, given in per cent.


Delay in diagnosis of oral squamous cell carcinoma; a report from The Netherlands.

The referral pattern, patients' and doctors' delay of a limited number of 50 patients suffering from oral squamous cell carcinoma have been investigated. The majority of the patients consulted the family doctor as the first source of help. The mean patients' and doctors' delay was 103 and 22 days, respectively the median being 35 and 11 days, respectively. The gender, dental status, site and tumour size did not show a significant correlation with the delay. Measures directed to the early detection of oral cancer should place special emphasis on the patients' delay.


[An assessment of the individual sensitivity of Wistar rats to the development of morphine dependence].

A search was made for behavioral and physiological indicators which could serve predictors of the individual sensitivity of Wistar rats to the development of physical morphine dependence. Animals with high sensitivity to the development of dependence initially demonstrated intensive ambulation and low motor rearing in the "open field" and had low nociception. Stable animals exhibited high ambulation and motor rearing with insignificant grooming activity as compared to other rats. It has been revealed that rats sensitive to the development of dependence demonstrate higher anxiety in the Vogel test as compared to the stable ones. The findings obtained allowed one to derive a number of equations to predict Wistar rats' individual sensitivity to the development of physical morphine dependence.


Hodgkin's disease involving the gingiva in AIDS.

Non-Hodgkin lymphomas are a recognised complication of AIDS and may involve the oral cavity. However, no case of Hodgkin's disease affecting the oral cavity in AIDS appears to have been recorded. We report a male homosexual with AIDS and Hodgkin's lymphoma, who presented with gingival involvement.


Smoking, alcohol, dentition and diet in the epidemiology of oral cancer.

This matched case-control study was conducted in Western New York. The smoking, alcohol consumption, dental hygiene and diet of 290 cases were compared with those of 290 sex-, age-, and neighbourhood-matched controls. The results confirm earlier findings that cigarette smoking and alcohol consumption impart substantial risk of oral cancer. The results also confirm that poor oral hygiene increases the risk of oral cancer, although this effect is much smaller than those of cigarette smoking and alcohol consumption. The results suggest that, of macronutrients, intake of fat is more likely than those of protein or carbohydrate to be related to risk. Of micronutrients, calcium, sodium, riboflavin and retinol are associated with risk, while thiamin, niacin, and dietary fibre are associated with decreased risk. Although patterns of dietary effects are discernable, these effects are in general much weaker than are those of smoking and alcohol consumption.


Hepatic veno-occlusive disease--liver toxicity syndrome after bone marrow transplantation.

Hepatic veno-occlusive disease (VOD) is the most common life threatening complication of preparative-regimen-related toxicity for bone marrow transplantation (BMT). The frequency of VOD varies greatly, from 1-2% in centers performing pediatric BMT for thalassemia to over 50% in some centers doing BMT for hematologic malignancy. The term liver toxicity syndrome is a clinicopathologic definition which encompasses the range of histopathology within the hepatic venules and surrounding sinusoids and hepatocytes. These histologic abnormalities are statistically associated with a clinical syndrome of jaundice, ascites, and painful hepatomegaly developing early post-transplant. Newer modalities which may aid accuracy are transvenous liver biopsy along with determination of the gradient between the wedged and free hepatic venous pressures, and measurement of blood coagulatory components, particularly protein C levels. Analyses of clinical risk factors for VOD are confounded by lack of a clear hierarchy of risk when comparing heterogeneous patient populations, the methods of patient selection and choice of controls, and whether analysis is univariate or multivariate. Prospective multivariate analyses indicate that the risk of developing liver toxicity is independently correlated with intensity of conditioning therapy, pre-transplant viral hepatitis, use of antimicrobial therapy with acyclovir, amphotericin, or vancomycin (reflecting fever), and mismatched or unrelated allogeneic marrow grafts. These analyses plus morphologic and biochemical data support the hypothesis that VOD is caused by cytoreductive injury to hepatocytes and endothelium in zone three of the liver acinus, and in turn strongly influenced by factors which induce the release of tumor necrosis factor-alpha (TNF-alpha) leading to enhancement or activation of coagulation with obstruction of hepatic sinusoids and venules. Pharmacokinetic measurements of busulfan as a conditioning agent demonstrate a correlation between high steady-state busulfan levels and liver toxicity and suggest that safer and/or more efficacious plasma busulfan concentrations can be obtained by making individual dose adjustments and by changing the schedule of administration. Conservative therapy of severe VOD, including the use of peritoneal-pleural shunts for relief of ascites, is unsatisfactory. Results from prophylactic studies aimed at preventing VOD by heparin or prostaglandin E1 indicate considerable differences with toxicity and efficacy. Use of the TNF-alpha blocker, pentoxifylline, has also shown promise in lessening VOD. A statistical model which predicts patients likely to have an unfavorable outcome from VOD has been used to select premorbid patients for promising new therapeutic modalities, such as recombinant tissue plasminogen activator.


Antimitochondrial antibodies in patients with chronic graft-versus-host disease.

Chronic graft-versus-host disease (cGVHD) and primary biliary cirrhosis (PBC) have many clinical and laboratory features in common. These include scleroderma or lupus erythematosus-like skin lesions, a Sjögren-like sicca syndrome, cholestatic liver disease and a variety of serological autoimmune phenomena. Furthermore, liver histology in both diseases is characterized by lymphocytic infiltration of the portal fields and destruction of small bile ducts. We investigated whether there were also parallels between both diseases in incidence and characteristics of antimitochondrial (AMA) and other autoantibodies. Sera from patients with cGVHD (n = 11, group 1) were examined by immunofluorescence (IFL) and immunoblot (IBL), and the results were compared with sera from patients without cGVHD (n = 21, group 2) and after autologous BMT (n = 16, group 3). In group 1 AMA was detected by IFL in one and by IBL in nine of 11 (81%) patients. Group 2 and 3 patients were AMA-negative by IFL and AMA positive by IBL in statistically lower incidence of 19% and 6% (p less than 0.001), respectively. cGVHD-associated AMA recognized a spectrum of mitochondrial proteins, the most frequent being molecules of 63/60 kD and 22 kD. Follow-up studies showed a temporal correlation between the emergence of AMA and the clinical occurrence of cGVHD. We conclude that patients with cGVHD have a high incidence of AMA similar to patients with PBC, but the reaction pattern of AMA differs between the diseases. The presence of AMA in cGVHD further emphasizes the concept that both diseases may have a related pathogenetic background.


Fractionated TBI and methotrexate-cyclosporin do not seem to increase relapses in BMT for first chronic phase CML patients: results of a single centre study.

Fractionated total body irradiation (FTBI) and methotrexate-cyclosporin A(MTX-CSA) have been found useful in reducing interstitial pneumonia (IP) and acute graft-versus-host-disease (GVHD) in bone marrow transplantation patients, but an increase in relapse rate has been observed by some authors when these strategies are used. To evaluate this relapse risk, we performed a retrospective analysis in 24 consecutive first chronic phase chronic myeloid leukemia patients who received an HLA-identical non-T cell-depleted graft in a single institution. All were conditioned with cyclophosphamide plus FTBI (12 Gy in six fractions delivered twice daily for 3 days) (CY-FTBI) and received MTX-CSA as GVHD prophylaxis. Serial hematologic and cytogenetic bone marrow analysis were performed at least three times (days +30, +100, +360) and at variable intervals thereafter in long-term survivors. Actuarial probabilities of developing IP and acute GVHD greater than or equal to II were respectively 5.9% and 44.2%, with a GVHD-associated mortality of 33%. Four-year actuarial relapse and disease-free survival rates were 7.7% and 48.2% respectively. No exclusively cytogenetic relapses were observed. Our results suggest that CY-FTBI and MTX-CSA are not associated with an increase in relapse rate in 1CP-CML patients.


TCR gamma/delta positive lymphocytes after allogeneic bone marrow transplantation.

Peripheral gamma/delta+ T cells were studied in patients following allogeneic bone marrow transplantation (BMT) by indirect immunofluorescence utilizing two monoclonal antibodies (G1 and A13) able to recognize the two major subpopulations (V delta 2+ and V delta 1+, respectively) of these cells. We found that the relative percentage of 'total' (gamma/delta+ T lymphocytes) (V delta 2 + V delta 1 positive cells), and particularly of G1+ (V delta 2+) cells, in CD3+ lymphocytes was higher in transplanted patients, and especially in those presenting with acute graft-versus-host disease (aGVHD), than in normal controls. This finding was confirmed by the analysis of the V delta 2+/V delta 1+ cell ratio which was again significantly higher in patients with aGVHD as compared to controls. Similarly, the absolute number of 'total' gamma/delta+ and V delta 2+ cells was also significantly increased in patients with aGVHD. TCR gamma/delta+ T cells increased as a function of time after BMT reaching a plateau value at about day 60 post-BMT. When patients were stratified for the presence or absence of aGVHD this correlation was maintained only for patients with aGVHD. Finally, most V delta 2+ cells expressed surface T cell activation markers such as CD25 (IL-2 receptor) and DR (MHC class II) antigens. Our results suggest a possible involvement of gamma/delta+ T cells and particularly of V delta 2+ cells in the clinical and immunological events (aGVHD) occurring after allogeneic BMT.


Host origin of bone marrow fibroblasts following allogeneic bone marrow transplantation for chronic myeloid leukemia.

We investigated the origin of the fibroblastic compartment of stromal hematopoietic microenvironment in eight chronic myeloid leukemia (CML) patients following allogeneic BMT. At the time of the study, all eight CML patients showed complete and long-lasting (14-87 months) engraftment of donor hematopoiesis and absence of clonal Ph-positive hematopoiesis. The study was carried out using in vitro amplification of informative DNA sequences: a Y chromosome specific DNA fragment in three patients who received a sex-mismatched allograft, and locus D1S80, a variable number of tandem repeats polymorphism, in five patients who received a sex-matched allograft. In all cases bone marrow fibroblasts were of recipient origin. These data indicate that with current BMT procedures the stromal compartment of hematopoiesis is not transplantable in humans.


Predictive value of flow cytometric analyses of blast cells in assessing the phenotype of the leukemia colony-forming cell (L-CFC) population in acute myeloid leukemia.

Acute myeloid leukemia (AML) blast cells (BC) express antigens that are commonly found on their normal counterparts. The leukemia colony-forming cell (L-CFC) subpopulation, identified by its ability to form leukemia colonies in vitro, is thought to be the stem cell population that produces BC. To ascertain the association between myeloid antigens on the BC and the L-CFC from the same patient, we compared the expression of CD14, CD15, CD33, p124 and HLA class I from 17 cases of AML. These particular myeloid antigens were studied because they are suitable targets in purging bone marrow for autotransplantation. We found no significant difference in the expression of CD14, CD15, CD33, and HLA class I on the BC and L-CFC from the same patient, although we observed considerable heterogeneity among different AML cases. Analysis of the progenitor cell antigen p124 revealed significant within-patient differences on the BC and L-CFC (p = 0.007), with a greater tendency for expression on the L-CFC. This heterogeneity may be due to differences in maturation stage of the L-CFC and BC. This information is important when L-CFC phenotype is used to determine the appropriate selection of antibodies for purging of residual disease in the context of auto-transplantation.


Pneumocystis carinii pneumonitis following bone marrow transplantation.

Pneumocystis carinii pneumonitis (PCP) can occur in immunocompromised hosts, especially AIDS and cancer patients. Although recent research has focused on PCP in AIDS patients, few studies have described the clinical presentation of PCP in recipients of bone marrow transplantation (BMT). Between 1976 and 1991, of 1454 BMT patients at the University of Minnesota, PCP was documented in only 19. Eighteen of these had not been receiving PCP prophylaxis. Patients presented with a brief period (2-10 days) of symptoms including dyspnea, cough, and fever in greater than 75% of patients, but had only scant abnormal physical findings. Chest X-rays showed bilateral infiltrates in 58% of all patients, though 15% had no or minimal X-ray findings. Bronchoscopic alveolar lavage confirmed the diagnosis most often, but 13% of lavages were negative and required biopsy for the diagnosis. High dose trimethoprim-sulfamethoxazole was the initial treatment for 84% of the patients though 25% of these patients were later switched to pentamidine due to poor response or hypersensitivity reactions. Despite prompt diagnosis and therapy, overall survival was poor, with only 37% of patients surviving pneumonitis. Patients developing PCP less than 6 months post-BMT had greater mortality (89%) versus only 40% in later onset PCP (p less than 0.0001). Despite this better survival in the late-onset PCP cohort, the development of pneumonitis in these patients underscores the necessity for continued PCP prophylaxis beyond 1 year in some patients. Ongoing immunocompromise and need for prophylaxis should be appreciated in patients with graft-versus-host disease.(ABSTRACT TRUNCATED AT 250 WORDS)


Bone marrow transplants using volunteer donors--recommendations and requirements for a standardized practice throughout the world. The Executive Committee of the World Marrow Donor Association.

The World Marrow Donor Association, originally designated the Collaborative Marrow Donor Program, was established in 1988 to address problems and to establish guidelines in relation to 'international' bone marrow transplants--transplants in which the donor is in one country and the patient in another country. This paper sets out recommendations and requirements governing clinical indications, ethical considerations, selection and counselling of donors, collection and transportation of marrow and financial and insurance related issues.


Molecular remission occurring after donor leukocyte infusions for the treatment of relapsed chronic myelogenous leukemia after allogeneic bone marrow transplantation.

Donor leukocyte infusions were administered to a patient who had relapsed with chronic myelogenous leukemia after having failed two successive HLA-matched allogeneic bone marrow transplants. Serial cytogenetic, restriction fragment length polymorphism, and polymerase chain reaction studies of the patient's marrow and blood after receiving donor leukocyte infusions revealed disappearance of the leukemic clone and the establishment of complete donor chimerism. An antileukemic response in this patient occurred initially in the absence of clinically evident graft-versus-host disease (GVHD), but complete eradication of the leukemic clone did not occur until after the onset of GVHD. The patient is now 48 weeks post infusion and remains in complete remission. This case demonstrates that leukocyte infusions are an effective form of adoptive immunotherapy which can result in a sustained molecular remission.


Bronchiolitis obliterans organizing pneumonia as a complication of allogeneic bone marrow transplantation.

We report a patient who underwent two allogeneic bone marrow transplants for chronic myelogenous leukemia, initially in 1984 and again after relapse in 1990, who developed an identical pulmonary syndrome at a similar interval following each transplant. The patient presented with a non-productive cough, bilateral inspiratory crackles, and multiple patchy infiltrates on chest X-ray. Pulmonary function testing revealed a restrictive abnormality but no obstructive defects. The appearance of this pulmonary disorder after each transplant coincided with the development of chronic graft-versus-host disease. In both instances, this pulmonary syndrome completely reversed with corticosteroid therapy. The patient's chest computed tomographic scan and lung biopsy specimens were consistent with the diagnosis of bronchiolitis obliterans with organizing pneumonia (BOOP). While bronchiolitis obliterans has been reported following allogeneic transplant, BOOP has not previously been reported in this setting.


Comparative cost of allogeneic or autologous bone marrow transplantation and chemotherapy in patients with acute myeloid leukaemia in first remission.

We compared the direct costs of allogeneic bone marrow transplantation (Allo-BMT), autologous bone marrow transplantation (Auto-BMT) and chemotherapy (Chemo) in 40 adult patients under the age of 55 years with acute myeloid leukaemia (AML) in first complete remission (CR). Fourteen patients were treated with Allo-BMT, 11 with Auto-BMT and 15 with Chemo. These patients, who were part of two cooperative consecutive trials enrolling a total of 196 patients (BGM 84 and BGMT 87 studies), were those who were treated in the CHR Bordeaux and achieved CR after induction chemotherapy. Cost accounting extended over a maximum period of 5 years. The average cost of the procedure for a mean follow-up of 2 years and excluding the cost of treatment after relapse which eventually occurred was significantly higher for the Allo-BMT group (FF 392,724) and the Auto-BMT group (FF 393,461) than for the group that received Chemo (FF 128,947) (p < 0.00001). The average cost for the treatment of relapse was estimated at FF 266,436, irrespective of the previous treatment. The total cost, including the estimated cost of relapse according to its probability of occurring calculated from the original population, was significantly higher for the Allo-BMT group (FF 424,696; p < 0.01) and the Auto-BMT group (FF 505,364; p < 0.0001) than for the Chemo group (FF 304,846).(ABSTRACT TRUNCATED AT 250 WORDS)


Clinical characteristics of chronic cutaneous graft-versus-host disease in Japanese leukemia patients after bone marrow transplantation: low incidence and mild manifestations of skin lesions.

We investigated the incidence of chronic graft-versus-host disease (GVHD) and skin and oral lesions in chronic GVHD in 90 Japanese leukemia patients surviving over 100 days after bone marrow transplantation (BMT) from HLA-compatible siblings. The clinical characteristics of chronic cutaneous GVHD occurring in eight of these patients are summarized. There were some differences from previous reports in the USA and Europe. The incidence (8/29: 28%) of skin lesions in chronic GVHD was low in contrast to the previously reported high incidence (79-90%). Cutaneous manifestations in six out of eight patients with chronic GVHD tended to be mild, and lichen-planus-like eruptions in the skin and scleroderma-like lesions, which are well known as representative cutaneous manifestations of chronic GVHD, were rare. Furthermore, our statistical analysis indicated that there was no relationship between pretransplant total body irradiation and GVHD prophylaxis or acute GVHD and the onset of chronic cutaneous GVHD. The present study suggests that the differences from previous reports in the USA and Europe concerning chronic cutaneous GVHD may be attributable to differing genetic backgrounds in Japanese and western populations.


Urate metabolism during bone marrow transplantation.

We studied urate metabolism in 36 patients undergoing both allogeneic and autologous bone marrow transplantation (BMT) without allopurinol. Most patients had low tumour burdens. Three different preparative regimens were used; busulphan/cyclophosphamide (BUCY); BCNU, etoposide, ara-C and melphalan (BEAM) and cyclophosphamide/total body irradiation (CY/TBI). Urate excretion rose during each of the regimens but the pattern of excretion varied with each regimen. Urate excretion remained elevated 72 h after completion of BEAM and BUCY, possibly reflecting the prolonged action of some of the agents used, e.g. melphalan, busulphan and etoposide. Urinary urate concentrations were unchanged compared with pre-chemotherapy levels reflecting the adequacy of the hydration protocol. No significant rise in creatinine was seen and no cases of tumour lysis syndrome occurred. Serum uric acid levels were a poor reflection of urate production, falling in most patients, and are an unreliable end-point for decisions regarding prophylaxis. BMT can be safely undertaken in patients with low tumour loads without allopurinol if an adequate urine volume is maintained. In this series, high levels of urate excretion often persisted for 72 h after the completion of conditioning and adequate hydration should be ensured during this period.


Clonal imbalances of serum immunoglobulins after allogeneic bone marrow transplantation: an analysis by high-resolution two-dimensional gel electrophoresis.

The clonality pattern of immunoglobulins (Igs) produced after allogeneic bone marrow transplantation (BMT) was studied by high-resolution two-dimensional polyacrylamide gel electrophoresis (2D-PAGE) of serum samples and purified Igs. With this technique, the light (L) chain of a monoclonal Ig usually appears as a single spot. Thus, the degree of clonal diversity of the functional B cells can be appreciated by the electrophoretic pattern of the serum L chains. Furthermore, 2D-PAGE allows a semi-quantitative determination of prominent Ig clones according to the size of L chain spots. We found that serum electrophoretograms of 8/19 patients after BMT (5-9 months) revealed L chain patterns which were similar to those of normal polyclonal Igs, that is, less than five distinguishable small spots among a cloud-like indiscrete L chain spots region ('polyclonal' pattern). A spectrum of clonal abnormalities was observed on the electrophoretograms of 11/19 patients: in five patients, multiple small L chain spots (corresponding to Ig concentrations between 0.2 and 2 g/l) were detected ('oligoclonal' pattern), whereas in six others, 'typical' monoclonal Igs (Ig concentrations > 2 g/l) were observed with (3/19 patients) or without (3/19 patients) multiple small clonal components. Sequential analysis of serum obtained from patients at different times after BMT revealed that imbalanced clonal reconstitution was transient and evolved towards apparently normal polyclonal Ig production. Our observations show that the development of clonal 'gammopathies' after BMT is a frequent, but not obligatory phenomenon. It may reflect a transient restriction of the B cell repertoire either through a limited outgrowth of precursor cells or through selective antigenic pressures.


High-dose methylprednisolone therapy for acute graft-versus-host disease associated with matched unrelated donor bone marrow transplantation.

Acute graft-versus-host disease (aGVHD) is a major barrier to successful bone marrow transplantation (BMT) with matched unrelated donors. Eight of eight recipients of matched unrelated donor BMT developed aGVHD. We used a regimen of high-dose methylprednisolone (5 mg/kg/day for 4 days with responders continuing on treatment, and dose escalation to 10 mg/kg/day for non-responders) as initial therapy of aGVHD. One patient died on the second day of steroid administration. Each of the seven remaining patients responded to methylprednisolone, five at the 5 mg/kg/day dose and two at the 10 mg/kg/day dose. Three of five patients developed flare of aGVHD during reduction of the corticosteroid dosage and died with aGVHD and infection. Two patients have undergone reduction of methylprednisolone at a modified rate without a flare. Infectious complications during methylprednisolone treatment were very common and contributed to the death of the three patients with flare of aGVHD. Four patients in whom aGVHD was in remission survived serious systemic infections. High-dose methylprednisolone is effective initial therapy for aGVHD associated with matched unrelated BMT, but is associated with a high risk of serious infections.


Evaluation of pulmonary complications after bone marrow transplantation: the role of pretransplant pulmonary function tests.

To determine whether an association exists between abnormal pulmonary function tests (PFT) before bone marrow transplantation (BMT) and the rate of pulmonary complications after BMT, we retrospectively reviewed all transplants performed in our center between March 1984 and December 1990. A total of 163 patients, 15 years of age and older, with a hematologic malignancy or a solid tumor were treated with intensive therapy and autologous (118) or allogeneic (55) BMT. Sixty patients (37%) developed a pulmonary complication which contributed to patient death in 29 transplants (18%). Patients with pulmonary metastases, prior thoracotomy, or prior radiation to the chest had a higher frequency of abnormal PFT. By univariate analysis, patients with abnormal FVC, FEV1, or TLC before BMT had a significantly increased rate of pulmonary complications (p < 0.005). By multivariate analysis, the rate of pulmonary complications was significantly associated (p = 0.004) with abnormal FEV1 only: in the first 2 months after transplantation the rate was 65% in patients with FEV1 < 70% in contrast to 34% in patients with FEV1 > or = 70% (risk ratio = 1.9). There was no association, however, between abnormal pretransplant PFT and fatal pulmonary complications. We conclude that patients with pretransplant ventilatory defects have a higher risk of pulmonary complications after BMT, but the incidence of fatal complications was not significantly increased, although we cannot exclude a diminished study power due to the sample size. We believe that patients with abnormal PFT should not be excluded from transplantation if the anticipated anti-tumor effect is estimated to be substantial, but additional preventive measures may be necessary.


Pilot trial of prophylactic ursodiol to decrease the incidence of veno-occlusive disease of the liver in allogeneic bone marrow transplant patients.

Ursodiol is a hydrophilic, non-hepatotoxic bile salt indicated for the medical treatment of cholesterol gallstones. This pilot study explored the use of prophylactic ursodiol in an attempt to decrease the incidence and severity of veno-occlusive disease (VOD) of the liver following allogeneic bone marrow transplantation (BMT). Between February 1991 and January 1992, 22 consecutive patients undergoing BMT for hematologic malignancies received the BU(4)/CY(2) preparative regimen and CSA/MTX for GVHD prophylaxis. Ursodiol, 600-900 mg daily by mouth was begun at least 1 day prior to beginning the preparative regimen. Results for this pilot group were compared to a control group of 28 consecutive patients transplanted between June 1989 and January 1991 with the same regimen without ursodiol. There were no significant differences in disease or clinical status between the groups pretransplant. However, mean baseline AST levels were significantly higher in the ursodiol group, 28.0 U/l vs 18.1 U/l in the control group (p = 0.001). The median maximum bilirubin observed post-transplant was 2.35 mg/dl (range 0.9-45) in the ursodiol group, and 5.05 mg/dl (range 0.7-29.4) in controls. The incidence of VOD was 2/22 (9.1%) in the ursodiol group and 18/28 (64.3%) in controls (p = 0.0001). Death due to VOD occurred in 1/22 patients (4.5%) in the ursodiol group and in 6/28 (21.4%) controls (p = 0.12). Our data suggest that ursodiol may decrease the incidence of VOD in allogeneic BMT patients.


Congenital sideroblastic anemia successfully treated by allogeneic bone marrow transplantation.

Allogeneic bone marrow transplantation (BMT) was carried out on a 34-month-old boy with congenital sideroblastic anemia. The patient had been red blood cell transfusion dependent since the age of 7 weeks. He did not respond to therapy with pyridoxine and developed secondary progressive hemosiderosis. The preparatory regimen consisted of busulfan (3.5 mg/kg for 4 days) and cyclophosphamide (50 mg/kg for 4 days). Full engraftment of donor bone marrow was achieved and effective hemopoiesis is still maintained 3 years after BMT.


Bullous pemphigoid associated with acute graft-versus-host disease after allogeneic bone marrow transplantation.

A 47-year-old patient was treated with allogeneic bone marrow transplantation (BMT) for chronic myelogenous leukaemia in blast crisis. Three months after the procedure he developed bullous pemphigoid (BP) and symptoms suggestive of BP oesophageal involvement, associated with skin and liver acute graft-versus-host disease. The occurrence of BP is exceptional after BMT.


Successful T cell-depleted allogeneic bone marrow transplantation in a child with recurrent multiple extramedullary plasmacytomas.

Multiple plasmacytomas with IgA paraproteinemia, a low grade lymphoid neoplasm of differentiated B cells rarely seen in the young, were encountered in a 10-year-old child. T cell-depleted allogeneic bone marrow transplantation (BMT) was performed because of progressive disease despite chemotherapy. Donor T cells were infused after transplantation in gradually increasing numbers to achieve a graft-versus-tumor effect. Complete eradication of all tumor masses was achieved following BMT with normalization of serum immunoglobulin levels. The patient remains in complete remission 4 years after BMT. Allogeneic BMT should be considered early in the course of low-grade lymphoid malignancy in the younger age group.


Encephalopathy and seizures induced by intravesical alum irrigations.

Hemorrhagic cystitis is a significant toxic effect of cyclophosphamide therapy. Continuous bladder irrigation of a 1% alum solution is a simple and generally safe method of chemical cautery to treat the bleeding urothelium. We report four cases of encephalopathy coincident with elevated aluminum levels as well as one patient who developed seizures while receiving continuous bladder irrigations with alum. All patients had significant renal insufficiency. We recommend the cautious use of alum irrigation in patients with renal impairment and monitoring of serum aluminum levels to prevent excessive accumulation and toxicity.


Relapse of acute leukemia presenting as acute cholecystitis following bone marrow transplantation.

Though included in the differential diagnosis of jaundice and abdominal pain, acute acalculous cholecystitis is an uncommon hepatobiliary complication of bone marrow transplantation. Leukemic infiltration of the gallbladder presenting as acute cholecystitis is rare. We describe two cases of acute cholecystitis following marrow transplantation that represented an unexpected relapse with leukemic infiltration of the gallbladder wall.


Hematologic relapse of chronic myelogenous leukemia following allogeneic bone marrow transplantation: apparent graft-versus-leukemia effect following abrupt discontinuation of immunosuppression.

Two patients with hematologic relapse of chronic myelogenous leukemia (CML) following allogeneic BMT were treated by abrupt discontinuation of cyclosporine. Both patients rapidly attained complete hematologic and cytogenetic remission and remain free of disease with long follow-up. In the first patient, disappearance of CML was associated with the development of graft-versus-host disease (GVHD). In the second patient GVHD did not develop until after clearing of disease had been documented by cytogenetic analysis. Laboratory studies in the second patient disclosed the presence of lytic activity against both K562 and autologous CML cells that enhanced with IL2. Correlation with serial immunophenotyping data from this patient suggests that the effector for this graft-versus-leukemia (GVL) reaction could have been a T lymphocyte. Abrupt discontinuation of post-transplant immunosuppression with cyclosporine may represent a therapeutic approach to CML which has recurred following BMT. Moreover, investigation of this clinical phenomenon in subsequent cases may permit direct study of the cellular mechanisms involved in the GVL effect.


Syndrome--a changing concept.

Syndrome is one of the oldest terms in the medical vocabulary. Traditionally, the term has been used mainly as a designation for complex medical entities, such as multiple abnormalities, that are characterized by clusters of concurring symptoms, usually three or more. During the mid-twentieth century, the meaning and the use of the term were altered. First to take place was an attempt to eliminate physicians' names from syndrome nomenclature, resulting in a significant increase in the use of descriptive designations in proportion to eponyms. But the trend was counterbalanced by the creation of new classes of eponyms. Eponymous syndrome nomenclature now includes the names of literary characters, patients' surnames, subjects of famous paintings, famous persons, geographic locations, institutions, biblical figures, and mythological characters. This was followed by a relaxation in the scope of the definition of syndrome, wherein the term could also be used as a modifier indicating a special (sometimes unspecified) complexity of an already named pathological condition. Eventually syndrome changed from its original use as an exclusively medical term and came to mean anything unusual, abnormal, bizarre, or humorous, whether medical, social, behavioral, or cultural. This unrestrained use of the term is the principal cause of an enormous volume of the sometimes irrelevant syndrome literature cluttering databases in the MEDLARS system and of the deterioration of "SYNDROME" as a specific MeSH term and a useful search parameter.


The characteristics of medical retraction notices.

During the past twenty years, more than ninety retraction notices have been published in biomedical journals. These retractions constitute a unique body of literature that biomedical researchers, bibliographers, and librarians must monitor to reduce scientific use of retracted, invalid papers. An analysis of medical retraction notices shows that very few are prominent in style, format, or placement, in spite of authoritative publication standards formulated by the International Council of Medical Journal Editors. Although researchers are ultimately responsible for the validity of the information they cite in their own publications, biomedical librarians are in a unique position to educate their patrons regarding retracted papers.


Using BITNET to access the National Library of Medicine databases.

An ongoing developmental project is described that uses the National Library of Medicine (NLM) GRATEFUL MED software on the BITNET network to access the NLM databases. The objective of the project is to improve biomedical communication capabilities to support health professionals in countries where international telecommunication services are limited. After a successful demonstration of the concept, the system was assembled and tested by the University of Chile and NLM. The full impact of this project will be measured at a later time. This paper describes the concept and testing of the system in Latin American countries.


Research in health sciences library and information science: a quantitative analysis.

A content analysis of research articles published between 1966 and 1990 in the Bulletin of the Medical Library Association was undertaken. Four specific questions were addressed: What subjects are of interest to health sciences librarians? Who is conducting this research? How do health sciences librarians conduct their research? Do health sciences librarians obtain funding for their research activities? Bibliometric characteristics of the research articles are described and compared to characteristics of research in library and information science as a whole in terms of subject and methodology. General findings were that most research in health sciences librarianship is conducted by librarians affiliated with academic health sciences libraries (51.8%); most deals with an applied (45.7%) or a theoretical (29.2%) topic; survey (41.0%) or observational (20.7%) research methodologies are used; descriptive quantitative analytical techniques are used (83.5%); and over 25% of research is funded. The average number of authors was 1.85, average article length was 7.25 pages, and average number of citations per article was 9.23. These findings are consistent with those reported in the general library and information science literature for the most part, although specific differences do exist in methodological and analytical areas.


Total quality management (TQM) in a hospital library: identifying service benchmarks.

Hospitals are turning to total quality management (TQM) to lower costs of providing care. A hospital library in a TQM environment needs to embrace corporate goals while maintaining its accountability as a contributor to quality patient care. Alliant Health System (AHS) Library at Norton Hospital and Kosair Children's Hospital in Louisville, Kentucky, conducted a study to establish TQM benchmarks and to examine the significance of its role in clinical care. Using a methodology designed to allow both library user and nonuser to respond, 2,091 surveys were distributed to physicians and nursing and allied health personnel. Areas surveyed included frequency of library use, impact of information received on clinical judgments, cognitive value of the information, and satisfaction with library products and services. Results confirm that the library has a substantial clinical role. Eighty-eight percent of reporting physicians agreed that information from the library contributed to higher quality care. Nursing and allied health were less convinced of the importance of the library's clinical role. Sixty-nine percent of nursing personnel and 58% of allied health personnel agreed that the library contributed to higher quality care. Nursing and allied health personnel also used the library less frequently than physicians. With these results as benchmarks, improving the clinical role of the library will take commitment to the TQM process and a willingness to change.


Factors influencing research productivity among health sciences librarians.

Secondary analysis was performed of data collected in 1989 from a random sample of members of the Medical Library Association. Results show that about half the sample had at least one publication; academic health sciences librarians were much more likely than hospital librarians to have published. Almost half the sample had taken formal courses in research, but only a small percentage had taken continuing education (CE) courses in research. Institutional support services for research were most available in academic settings. The combination of institutional support, CE training, and research courses explained 31.1% of the variation in research productivity among academic librarians; these factors were less important in hospitals and other institutional settings. The authors suggest that health sciences librarians working outside academia should seek support for research from sources outside the employing institution.


The landmark citation method: analysis of a citation pattern as a collection assessment method.

The landmark citation method is a new collection assessment method based on the citation record of a single landmark article. This citation record is developed by identifying sources which cite the landmark article. A bibliography, extracted from the citation record, is then used to complete an assessment of the collection. This method was developed and used to assess the biotechnology collection of the National Library of Medicine. The information gained from this study, in addition to demonstrating the technique, also provided insight into the evolution of the biotechnology literature.


Dial-in access to CD-ROM databases: beyond the local area network.

Although it has meant additional work, CDLink has enhanced the productivity and effectiveness of the library's public services program. CDLink enables the library to offer dial-in access to databases, either in CD-ROM or other MS-DOS formats. The VAX MS-DOS connection is a cost-effective way to combine the benefits of remote access and multiple simultaneous use. From the user's perspective, CDLink provides free, twenty-four-hour remote access to databases in a friendly, menu-driven environment. For the library staff, the CDLink service represents the achievement of a long-awaited goal.


A decade of AIDS literature.

From 1983 through mid-1991, more than 200,000 MEDLINE entries were AIDS-related. Close to 60% of the journals indexed in MEDLINE published at least one article on AIDS during the past ten years. As reflected by a subset of 29,077 MEDLINE records, the literature of AIDS has grown to encompass 29 languages and 65 countries. A bibliometric study of the medical literature helps to demonstrate the progression of AIDS as a world health problem and the concomitant expansion of the research effort underway to control it.


[Control of renal tubular regeneration].

Tubular necrosis induced by various drugs (aminoglycosides, platinum-based anticancer agents) elicits a process of renal tissue repair which involves an increase of cell turnover. The proliferative response remains commensurate with the degree of tubular injury and occurs primarily in the area of tubular epithelium which has suffered injury. After acute renal necrosis, tubular regeneration is associated with a transient dedifferentiation of epithelial cells. This tissue reaction is controlled and leads in most cases to a complete reepithelialization of injured tubules and consequently to a full restoration of normal kidney functions. Recent experimental evidences suggest that EGF (Epidermal growth factor) plays a prominent role in the control of this repair process. By immunocytochemical and biochemical methods we have observed in regenerating kidneys a diminution of the membrane-bound precursor of EGF (prepro-EGF) in distal tubules. Concomitantly, by electron microscopy, EGF immunoreactivity is detected on basolateral membranes of proximal tubules. These experimental data suggest that EGF precursor might be converted into a low molecular weight diffusible factor. The latter is able to interact with the receptors localized on the basolateral membranes of proximal tubules and to induce the tissue repair process.


[Postoperative irradiation in pulmonary cancer?].

Postoperative radiation remains a controversial issue in the management of lung cancer. Despite a better local control, a major concern is always the possible late lung effects induced by high doses of radiation required to achieve this benefit. In our works, we have been able to show that with an adequate technique and the use of CT-scan for treatment planning, such high doses can safely be delivered. Furthermore, several prognostic factors were identified including the degree of mediastinal lymph node involvement.


The perversion of mothering: Munchausen syndrome by proxy.

Munchausen syndrome by proxy, in which a seemingly caring and concerned mother is simultaneously harming her child, can best be understood in terms of the mother's need for a relationship with a physician that is rooted in a profound sense of early abandonment. This understanding broadens the definition of perversions. The infant in this sadomasochistic interaction is dehumanized and is used as a fetishistic object to control the relationship. The author's literature review and case report provide the basis for his exploration of the historical, cultural, and psychological factors that both contribute to the development of the syndrome and conspire to deny its reality.


Perceptions of family functioning and the occurrence of childhood sexual abuse.

The wide variety of sequelae attributed to childhood sexual abuse has led some authors to posit that it is the complex interaction between the object-relational developmental world of the child and the event and nature of the abuse that determines the enduring effects of the abusive experience. The authors addressed this hypothesis by examining the correlation between the occurrence of childhood sexual abuse and subjects' perceptions of the nature of their childhood family. Results revealed significant differences in the subjects' recollections of family functioning based on abuse status. Abused subjects recalled families that were isolative, rigidly ruled in an authoritarian style, and unable to foster the development of autonomy in family members. The authors discuss the study results in light of the interactions between memories of the childhood family and the experience of sexual abuse.


Toward an experiential psychoanalytic approach to the Rorschach.

With a conceptual approach to the Rorschach, there is a strong tie between this test and a theory of personality that lies outside the test itself. Shifts in that personality theory can provide new concepts and formulations for understanding Rorschach data. Such shifts can also promote new and different ways of conceptualizing and using the test. The author contends that changes in psychoanalytic theory are currently facilitating a more experiential view of the Rorschach. He reviews the relationship between personality theory and Rorschach testing, discusses changes in psychoanalytic theory that are leading to a more experiential Rorschach psychology, and describes the meaning of an experiential approach to the Rorschach.


Specialized extended hospital treatment for borderline patients.

The intensive psychoanalytically oriented hospital treatment described by the authors was developed specifically for borderline patients. This unique treatment, an integrated multimodal approach, is based on the theory that the disturbed behaviors and relationships of borderline patients are manifestations of intrapsychic impairment. The authors use a detailed case report to illustrate how the theory is transformed into technical precepts and applied to all aspects of the treatment.


Distinguishing features of pseudocomplex partial seizures.

The authors identify common features in the clinical presentations of three patients whose pseudoseizures mimicked complex partial seizures. All three had suffered the recent traumatic loss of a significant love object, and all manifested unconscious feelings of guilt and the use of defense mechanisms of denial, dissociation, introjection, identification, and symbolization. The authors explore the diagnostic, treatment, and etiological implications of these findings.


A psychodynamic approach to the master treatment plan.

Formulating master treatment plans for the hospital treatment of psychiatric patients is especially challenging to psychodynamically oriented clinicians unaccustomed to reducing complex intrapsychic and interpersonal phenomena to specific observable behaviors. In collaboration with a wide cross section of hospital staff members, the authors developed a conceptual framework for treatment plans compatible with psychodynamic thinking. They describe the treatment evaluation research from which the format of the treatment plan evolved, as well as the guide they developed to facilitate its implementation .


The influence of religion on sexuality: implications for sex therapy.

Religious beliefs are among the many factors that determine whether sexually dysfunctional persons will seek out a sex therapist. These beliefs may also generate resistance to therapy or influence patients to drop out of treatment before it is complete. Therapists who are sensitive to patients' religious beliefs enhance the likelihood of a successful treatment process. The authors present six case examples from their practice in which religious beliefs played an important role. They urge sex therapists to become more aware of the religious dynamic and to help address the paucity of clinical case material in the literature.


Radiological assessment of varicose veins.

Most patients with straightforward varicose veins only require a careful clinical examination combined with Doppler ultrasound scanning. When varicose veins are secondary to past deep venous thrombosis, recur after treatment or are associated with congenital anomalies, radiology is useful for diagnosis and management.


Psychotherapy of schizophrenia.

Recent developments in the psychotherapy of schizophrenia have integrated educational methods, skills training, family-based stress management and specific cognitive-behavioural strategies with optimal pharmacotherapy. These approaches have demonstrated considerable promise in alleviating the impairments, disabilities and handicaps associated with schizophrenia.


Clinical applications of flow cytometry.

Flow cytometers allow the rapid, sensitive and quantitative measurement of cells, cell surface markers and cell nuclear components for research and clinical laboratory use. They are producing new insights in many branches of clinical science.


Towards good audit.

All doctors are enjoined to audit, yet there is concern that many audits do not improve patient care. Despite the profusion of audit methods, good audits have many features in common. This paper identifies these essential features, facilitating the appraisal of proposed or completed studies.


Guide to postgraduate exams: Royal College exams.

Postgraduate exams are important milestones (or barriers) in specialist careers. However, there are several peculiar features in the Royal Colleges' exams, and considerable differences between them. This is the first of three articles aimed at helping candidates make appropriate preparations.


Sarcoidosis.

Sarcoidosis is a multisystem disorder of unknown cause characterized by non-caseating granuloma formation and evidence of enhanced cellular immune response at the site of involvement. Although the majority of patients have a self-limiting illness, a significant proportion develop severe chronic disability.


Surgical treatment of urinary stress incontinence.

This article reviews traditional vaginal and suprapubic procedures as well as more recent advances such as urethral bulking agents and artificial sphincters. It illustrates how the chosen operation must be tailored to the individual patient and how the surgeon treating urinary incontinence requires a variety of procedures in his repertoire.


Exercise: the best therapy for intermittent claudication?

The prophylactic value of physical activity for arteriosclerotic diseases is generally accepted. Regular exercise is also the most effective therapy for intermittent claudication although drug treatment is more popular in general practice. Recent findings show that exercise and drug treatments complement each other.


Causes and management of dysphasia.

Dysphasia comprises a wide-ranging complex of linguistic impairments. Comprehensive and individual description of the verbal and non-verbal aspects is required for the tailoring of an approach to therapy and management.


Transport of the critically ill child.

The principles of stabilization before, and monitoring during, transportation are well established in adult intensive care practice but less so in paediatrics. The speed with which critically ill children deteriorate and the aggressiveness of treatment needed are often underestimated. A dedicated, fully funded and staffed transport service for each paediatric referral centre in the UK is urgently required.