Treatment of cutaneous squamous cell carcinomas by intralesional interferon alfa-2b therapy. Intralesional recombinant interferon alfa-2b has been shown to be effective in the treatment of actinic keratoses and basal cell carcinomas. This open-label study was designed to evaluate the effectiveness and cosmetic result of this therapy on actinically induced, primary cutaneous squamous cell carcinomas. Thirty-six squamous cell carcinomas (28 invasive lesions and 8 in situ lesions) ranging in size from 0.5 to 2.0 cm in the longest dimension were treated with interferon alfa-2b 1.5 million units injected intralesionally three times per week for 3 weeks. Eighteen weeks following therapy, the treatment sites were excised and examined for histologic evidence of remaining tumor. Thirty-three (97.1%) of 34 evaluable lesions revealed an absence of squamous cell carcinoma histologically after therapy, although three biopsy specimens (8.8%) obtained after treatment showed actinic keratoses, for an overall complete response rate of 88.2%. The lesion not eliminated after treatment was an invasive squamous cell carcinoma. The investigators and patients independently judged 93.9% of cases to have a very good or excellent cosmetic result. Adverse reactions were limited to those influenzalike symptoms well recognized to occur with interferon therapy and these were well tolerated. Only one patient discontinued therapy due to side effects. This trial demonstrates that intralesional interferon is effective in the treatment of small sun-induced squamous cell carcinomas with well-tolerated side effects and a highly acceptable cosmetic result.


U1RNP antibody-positive neonatal lupus. A report of two cases with immunogenetic studies. Neonatal lupus erythematosus (NLE) is a distinct subset of lupus characterized by cutaneous findings (50%), cardiac conduction defects (50%), and autoantibodies to Ro (SS-A) antigen. HLA typing studies of Ro (SS-A) antibody-positive mothers of infants with NLE have shown an association with the HLA-DR3 phenotype. We report the clinical and serologic features of two infant-mother pairs who are U1RNP antibody positive and Ro (SS-A) antibody negative. HLA typing is reported on these infants, their mothers, and two additional infant-mother pairs with U1RNP antibody-positive lupus whose clinical features have been reported previously. Cutaneous findings included malar erythema, annular and polycyclic plaques, and scales that resolved with residual telangiectasia and hyperpigmentation 6 months after birth. Systemic abnormalities, including complete heart block, were absent. HLA typing revealed HLA-DR3 in two of four mothers, HLA-DR4 and HLA-DRw53 in two of four mothers, and either HLA-DQ1 or HLA-DQ3 in four of four mothers. No distinct HLA associations were seen in the three infants examined. The spectrum of cutaneous disease in U1RNP antibody-positive infants is similar to Ro (SS-A) antibody-positive infants with NLE. Complete heart block was not a feature of U1RNP antibody-positive NLE. HLA typing studies show a more diverse immunogenetic pattern in U1RNP antibody-positive mothers of infants with NLE compared with Ro (SS-A) antibody-positive mothers.


Vesicular erythema migrans.

Vesicular erythema migrans. Lyme disease is the most common vector-borne disease in the United States. The characteristic rash, erythema migrans, is an early sign of the disease. Clinical criteria remain the "gold standard" for diagnosis at this stage of illness. Five (8%) of 65 patients with erythema migrans seen in a Lyme disease diagnostic center in Westchester County, New York, had a lesion with vesicles. Borrelia burgdorferi was cultured from two of five. In one case the positive culture came from a swab of the blister fluid. Recognition of erythema migrans and its variants is important, since early treatment of Lyme disease may prevent late complications. Vesicular erythema migrans should be added to the differential diagnosis of inflammatory vesicular rashes in the appropriate clinical setting.


Two cases of transfusion-associated graft-vs-host disease after open heart surgery. Some cases of blood transfusion-associated (TA) graft-vs-host disease (GVHD) in immunocompetent patients have been reported, but those dermatologic findings were not precisely mentioned. We describe patients with clinicopathologically TA-GVHD and compare TA-GVHD and acute GVHD after bone marrow transplantation. Two cases of TA-GVHD after open heart surgery are reported. In both immunocompetent patients, severe erythema multiformelike skin rash developed over the entire body, followed by fever, diarrhea, jaundice, transaminitis, pancytopenia, and marrow alpasia approximately 10 days after operation. The rash in one patient changed from erythema multiformelike to toxic epidermal necrolysis at death. Skin biopsy specimens revealed eosinophilic bodies, basal vacuolation, and exocytosis in the epidermis. Eosinophilic bodies tend to appear in the upper epidermis. Immunohistochemistry studies revealed that infiltrating cells were CD4 and CD8. While acute GVHD in immunosuppressed patients who have undergone bone marrow transplantations often shows lichenoid histologic features, TA-GVHD in our patients who were immunocompetent may resemble severe erythema multiforme or toxic epidermal necrolysis. The difference in TA-GVHD may be related to lack of host modification by immunosuppression. Irradiation of the blood products should be required in open heart surgery, for TA-GVHD in immunocompetent patients is almost always fatal.


Immune dysregulation in atopic eczema.

Immune dysregulation in atopic eczema. In this review, present knowledge of atopic eczema immunopathogenesis is summarized, emphasizing recent new findings. Systemic abnormalities in cell-mediated immunity have not been demonstrated firmly in patients with atopic eczema. Within the skin itself, there is evidence for decreased cell-mediated immunity, which is partially correlated with the severity of skin disease. Atopic eczema, however, cannot be regarded as a direct result of decreased cutaneous cell-mediated immunity, since immunophenotyping studies have revealed activated T cells as well as dendritic cells within involved skin. In addition, disease marker studies in peripheral blood indicate vigorous T-cell activation in atopic dermatitis. The original observation of IgE molecules on the membranes of Langerhans cells may indicate trapping of IgE allergen complexes, their processing, and subsequent presentation to allergen-specific T cells within involved skin. Recent findings as to the abnormal regulation of IgE synthesis in atopy point to a preferential expansion of interleukin 4 and interleukin 5 producing allergen-specific T cells, leading to increased production of interleukin 4 and thus increased levels of allergen-specific IgE. We have prepared atopic skin as well as peripheral blood-derived T-cell clones and determined their specificity and cytokine production profile. Results indicate in situ production of interleukin 4 and interleukin 5 within involved skin in response to environmental antigens. These new findings as to the basis of IgE dysregulation in atopy, as well as to the identification of an abnormal cytokine secretion pattern by T cells presumed to be central in immunopathogenesis of atopy-related disorders, suggest a distorted and cytokine-mediated self-perpetuating response of the skin immune system to environmental allergen(s) in the pathogenesis of skin disease in atopy. These observations may have important implications for the development of new therapies for atopic eczema.


Photoallergic contact dermatitis. Results of photopatch testing in New York, 1985 to 1990. Over a 6-year period, 187 patients with a history of photosensitivity were photopatch tested using standard techniques. Seventy-six patients were male and 111 were female. Most patients were white (151 patients). Two thirds of the patients were between the ages of 31 and 60 years. Testing revealed a total of 63 positive reactions: 14 plain contact, 41 photocontact, and eight combined contact and photocontact in 37 (20%) patients. Careful history taking resulted in a diagnosis of clinically relevant photoallergic contact dermatitis in 54% of these 37 patients or 11% (20) of the total tested. Ten of the relevant responses were due to fragrance ingredients (musk ambrette and 6-methylcoumarin); 18 were due to sunscreen agents (nine to p-aminobenzoic acid and esters, nine to oxybenzone). The fragrance reactions occurred in the early years of the study (1985, 1986, and 1987) while the sunscreen agents accounted for all but two of the 14 positive reactions in the last 3 years of the study (1988, 1989, and 1990). These data suggest that the incidence of photoallergy due to fragrances is declining, while reactions to sunscreen agents, in particular oxybenzone, are increasing. This trend may reflect an altered use pattern by the general population for products containing these chemicals.


Alopecia areata. A review of therapy, efficacy, safety, and mechanism. Although it is clear from the foregoing that some of the drugs and chemicals used to treat severe alopecia areata are efficacious to some degree, it is impossible to draw any meaningful comparisons among the data outlined in Tables 1 and 2. Virtually all of the studies were designed differently. Differences in chronicity and extent of disease as well as history of previous treatment resistance may significantly affect efficacy data even as two investigators compare the same drug. Drug-induced hair regrowth in alopecia areata may be very slow; a cosmetic response may take 1 to 2 years to achieve. Efficacy determinations made at shorter intervals may, therefore, not reflect true therapeutic potential. Efficacy end points vary significantly and need to be standardized. From a practical standpoint, scalp hair coverage that is deemed by the patient to be cosmetically acceptable seems to be a reasonable efficacy end point to report. Maintenance of cosmetic effect with continued treatment and/or following discontinuation of treatment also is useful to document. Table 3 outlines my approach to therapy of alopecia areata. Topical treatments often must be used for as long as 3 months before evidence of regrowth can be seen. In my experience with severe disease, if topical treatments cannot control a flare or induce regrowth, then the patient will often require either lengthy or frequent courses of systemic steroids. In my experience, prednisone doses as low as 20 mg/d may be associated with aseptic neurosis of the hip or severe gastrointestinal bleeding. Severe alopecia areata is a disease for which all therapies are, at best, palliative and, at worst, potentially harmful to patients who are usually otherwise very healthy. The psychosocial significance of this disease is enormous. The insights shared by a long-time sufferer of the disease mirror those expressed by the many patients with whom I have worked during the past 12 years. Three key elements to effectively treat the patient are (1) to help the patient understand the disease; (2) to encourage the patient to share his or her feelings with the physician, family, friends, and other sufferers of the disease; and (3) to help the patient to maintain a sense of hope for future scientific knowledge and treatment of the disease. With a thorough knowledge of the potential benefits and risks of each treatment or combination treatment, the physician with the patient's understanding and cooperation may then embark on what may be in severe cases a lengthy and sometimes unproductive therapeutic process.


Effects of oral and intramuscular vitamin K prophylaxis on vitamin K1, PIVKA-II, and clotting factors in breast fed infants. A randomised clinical trial was conducted to establish the effects of oral and intramuscular administration of vitamin K at birth on plasma concentrations of vitamin K1, proteins induced by vitamin K absence (PIVKA-II), and clotting factors. Two groups of about 165 healthy breast fed infants who received at random 1 mg vitamin K1 orally or intramuscularly after birth were studied at 2 weeks and 1 and 3 months of age. Although vitamin K1 concentrations were statistically significantly higher in the intramuscular group, blood coagulability, activities of factors VII and X and PIVKA-II concentrations did not reveal any difference between the two groups. At 2 weeks of age vitamin K1 concentrations were raised compared with reported unsupplemented concentrations and no PIVKA-II was detectable. At 3 months vitamin K1 concentrations were back at unsupplemented values and PIVKA-II was detectable in 11.5% of infants. Therefore, a repeated oral prophylaxis will be necessary to completely prevent (biochemical) vitamin K deficiency beyond the age of 1 month.


Oscillations of body temperature at night. There is increasing evidence that overheating is a contributing factor for some cot deaths. One hypothesis is that infant thermoregulation is closely related to respiratory control. To test this hypothesis it was necessary to determine the normal pattern of body temperature in the developing infant. A system has been designed and built to record continuously temperature signals from ambient, rectal, and various skin site sensors. Overnight studies were performed on 30 infants aged between 2 and 26 weeks in a hospital ward. Various time and frequency domain analyses of the temperature data have been developed. Analysis of body temperature rhythms has confirmed patterns during sleep which mature with age. In addition a periodic oscillation of body temperature has been found with a cycle of approximately one hour. This oscillation may reflect sleep state and its further study may give an insight into control of infant thermoregulation and the integration of this control with that of breathing and the cardiovascular system.


Factors affecting the development of night time temperature rhythms. The rectal temperature of 26 infants between 6 and 16 weeks old was monitored continuously for one night each week. Rectal temperature always decreased with sleep but the minimum temperature attained changed with age. Some time between 8 and 16 weeks old the minimum sleeping rectal temperature decreased abruptly from around 36.8 degrees C to around 36.4 degrees C. This change was complete within one week and did not normally revert unless the infant became ill. Some infants changed as early as 8 weeks old, others not until 16 weeks. Breast fed infants changed significantly earlier than bottle fed infants. Girls changed significantly earlier than boys. First born infants changed significantly earlier than second or subsequent infants. Early changes were significantly more likely to be sleeping lateral or supine, and to have older mothers. They tended to come from more affluent families. There was no association between the time of change and the thermal environment in which the infant slept or the number of episodes of minor illness in the early weeks of life.


Paediatric cardiac transplantation with steroid-sparing maintenance immunosuppression. In order to determine the results of steroid-sparing maintenance immunosuppression in paediatric patients who have undergone orthotopic heart transplantation (OHT), a retrospective study was undertaken in 12 children and five infants (median age 3.5 years). Preoperative diagnoses were cardiomyopathy in seven and congenital heart disease in 10 patients. Immunosuppression was induced by cyclosporin, azathioprine, methylprednisolone, and antihuman lymphocyte immune globulin. It was maintained with cyclosporin and azathioprine. After induction, five patients received no further steroids. The remainder, except one, required only pulses for rejection (13 episodes or 0.51 episodes/patient year). Long term complications included hypertension in six, and renal impairment in three children. There were no early or late deaths from infection. Actuarial survival was 94% at one year. Of the children followed up for more than one year, all demonstrated an increase in height SD scores (mean (SD) -2.15 (1.35) to -1.15 (1.16)). We conclude that a steroid-sparing maintenance immunosuppression regimen can be successfully employed in paediatric OHT, and that significant catch-up growth can be achieved postoperatively.


Intravenous immunoglobulin in HIV-I infected haemophilic patients. In order to evaluate the efficacy of intravenous immunoglobulin (IVIG) in the early stages of HIV infection (patients without AIDS or AIDS related complex) a prospective controlled open trial was conducted in 36 patients (age 6-19 years) with haemophilia. Eighteen patients received 0.3 g/kg IVIG at two week intervals; 18 patients served as controls. Major criteria for the evaluation were progression of HIV disease assessed by the modified Brodt/Helm classification, number of infectious events and HIV associated thrombocytopenia, and the CD4+ T cell count. After 24 months of evaluation seven patients in the IVIG group and five patients in the control group deteriorated according to their staging, with one patient in each group developing AIDS. Thrombocytopenia and infectious events, but no severe bacterial infections, occurred in both groups in similar numbers. The absolute CD4+ T cell count decreased by 284/microliters in the IVIG group and by 143/microliters in the control group respectively (mean values). The statistical analysis of these criteria did not reveal any significant difference. In conclusion, IVIG was not effective in the early stages of HIV infection in patients with haemophilia. IVIG did not slow down the progression of HIV disease and did not prevent the development of an immunodeficiency as assessed by the CD4+ T cell count.


Gastrointestinal complications of gastrocystoplasty. The cases are reported of five children with chronic renal failure who underwent gastrocystoplasty for a variety of urological disorders. Gastrocystoplasty comprises the transplantation of a vascularised segment of stomach to the bladder to form an augmented neobladder. The patients had gastrointestinal complications after the operation, including considerable weight loss in all five patients, accompanied by marked failure to thrive in four of the five patients, and food aversion, feeding intolerance, dumping syndrome, delayed gastric emptying, and oesophagitis in two patients. Three of the five patients developed severe abdominal pain and haemorrhagic cystitis secondary to gastric acid secretion in the neobladder from the transplanted gastric pedicle. Nutritional and pharmacological interventions were used to manage the gastrointestinal problems. Explanations are offered for the pathophysiology of the observed complications of gastrocystoplasty. It is believed that the use of this procedure in infants and children, particularly those with chronic renal failure and uraemia, warrants caution until successful long term follow up and experience with this procedure have been reported.


Prepubertal height velocity references over a wide age range. In order to correct height velocities for the confounders age and sex, SD scores can be calculated using the mean and the SD of the height velocity in the normal population. However, current methods are inappropriate for prepubertal children in the age range in which puberty occurs, because reference groups then consist of a mixed prepubertal/pubertal population. The mathematical infancy-childhood-puberty (ICP) model opens up the possibility of dissecting the puberty component from the total growth curve. New references for height velocity for prepubertal children calculated over a 12 month interval up to the ages of 15.5 years (boys) and 13.5 years (girls) have been constructed on the basis of adaptations of the ICP model and the Swedish longitudinal growth study.


Bone age, social deprivation, and single parent families. It is well known that deprivation affects bone growth. The study was set up to investigate what aspects of deprivation are of greatest importance. Bone ages of 1593 child trauma patients aged 0-19 years from Middlesbrough General Hospital, Cleveland, were related to local authority ward indices of socioeconomic status (51 wards). After adjustment for chronological age and sex, the mean bone ages in each ward were highly significantly negatively associated with five ward indices of deprivation: the rate of single parent families, low care ownership, unemployment, rented housing, and overcrowding. There was a mean four month deficit in bone age among children living in wards with the highest single parent family rates. The inverse association between deprivation and bone age is unlikely to be causal throughout childhood, as older and younger children were affected to the same extent. However the bone age deficit could be caused by deprivation retarding skeletal maturation during a critical period in early life.


Centiles for adult head circumference.

Centiles for adult head circumference. Reference range for head circumference on the Tanner charts do not go beyond age 16. In this study the head circumference and heights of 354 adults in two British centres were measured. The centile charts constructed from these measurements show that adult head circumference is related to height. The mean head circumference of a male of average height is above the 97th centile for a 16 year old on the Tanner charts. The paediatric charts are therefore inappropriate for use in adult males.


Immunisation status in inner London primary schools. In one inner London district health authority, the immunisation status of children attending their routine school entry health interview was reviewed over four terms. During the course of these interviews, school nurses completed a questionnaire with parents that asked for their child's immunisation history and details of family and social background. Parental reporting of immunisation history was compared with district health authority records. Only 56% of children reviewed were found to be fully immunised, although a substantial number (386) of the 513 partially immunised children required only a preschool booster. Four percent (54) of the children had received no immunisations; a disproportionately high number of these were recent immigrants. Mechanisms for identifying unimmunised children before they enter communal groups need to be established.


An audit of preschool vision screening.

An audit of preschool vision screening. An audit was carried out to clarify the dispute surrounding the vision screening test at 3.5 years. The uptake was 53.5%, sensitivity 77%, specificity 96%, and positive predictive value 50%. In particular the uptake was poor and the test needed a clear policy for the future.


Microfollicular thyroid adenoma and congenital goitrous hypothyroidism. Three patients with congenital goitrous hypothyroidism are reported. They were treated with adequate thyroxine replacement and developed well defined microfollicular thyroid adenomas despite being euthyroid clinically and biochemically throughout their clinical course. Patients with congenital goitrous hypothyroidism appear to be at increased risk of developing thyroid adenoma in childhood despite the use of replacement thyroxine treatment in physiological doses.


Investigation of metabolic disorders resembling Reye's syndrome. Ten per cent of patients initially reported with Reye's syndrome in the British Isles (1981-91) were subsequently found to have an underlying inherited metabolic disorder (IMD). There was also evidence to suggest that other cases may not have been recognised. The range of metabolic disorders that mimic Reye's syndrome is wide and specialist, often complex, investigations are required to make a specific diagnosis. Those patients presenting with Reye's syndrome-like illness but also with one or more clinical features suggestive of an IMD require particular attention and detailed investigation. Recommendations for specimen collection and investigation are presented.


Renal function in sick very low birthweight infants: 1. Glomerular filtration rate. A total of 135 measurements of polyfructoside clearance as a measure of glomerular filtration rate (GFR) were made in 39 infants of 25.5-33 weeks' gestation, birth weight 720-2000 g, between the ages of 0.5 and 33 days. GRF was related to postconceptional age and increased exponentially from geometric mean 0.59 ml/min at 26 weeks' postconceptional age to 1.40 ml/min at 33 weeks. GFR in the first week and GFR at later ages were the same for a given postconceptional age. GFR was the same in sick infants with severe ventilatory failure as in less ill infants. There was no evidence that GFR was influenced by nitrogen input. GFR increases postnatally in a preprogrammed way irrespective of other postnatal events. When factored by body weight GFR in the first week increased only little from arithmetic mean 0.70 ml/min/kg at 26 weeks to 0.84 ml/min/kg at 33 weeks, but older infants often had a falsely high GFR per kg when they lost weight in the first week or two after birth or failed to gain weight later.


Renal function in sick very low birthweight infants: 2. Urea and creatinine excretion. Plasma urea and creatinine concentrations and urea and creatinine clearances and excretion were measured in a sample of 40 infants of 25.5-33 weeks' gestation, birth weight 720-2000 g, between the ages of 0.5 and 33 days. Creatinine excretion rate was between 60 and 120 mumol/kg/day in the first five postnatal weeks (mean 90.5) and was independent of sex or growth retardation. This can be used in clinical practice to estimate instantaneous urine flow rate V, if the creatinine concentration is measured in a randomly voided urine sample, from the formula V = 90.5/urine creatinine, with 95% confidence limits +/- 39%. There is a wide range of plasma creatinine at all gestations and ages decreasing from range 75-130 mumol/l in the first two days to 35-80 mumol/l at 3 weeks of age. Plasma urea is a poor indicator of glomerular filtration rate (GFR) in sick preterm infants. GFR (ml/min/kg) can be estimated from plasma creatinine from the formula GFR = 69.2/plasma creatinine but this estimate is imprecise with 95% confidence limits +/- 46%. Urea:creatinine clearance ratio was usually less than 1.0 (range 0.18 to 1.5) and was lower when the urine flow rate was low. Urea excretion was up to 17 mmol/kg/day in the first two weeks, higher in the more immature infants. These high levels were paralleled by a high plasma urea concentration, up to 18 mmol/l. A high plasma urea is not necessarily associated with renal failure or dehydration.


Renal function in sick very low birthweight infants: 3. Sodium, potassium, and water excretion. Renal excretion of sodium, water, and potassium was measured on 434 occasions in a sample of 40 infants of 25.5-33 weeks' gestation, birth weight 720-2000 g, between the ages of 0.5 and 36 days. Water excretion varied between 1% and 30% of the glomerular filtration rate, or 15-350 ml/kg/day, and varied widely from day to day in individual infants. Nearly all infants became hyponatraemic before or after the first postnatal week. There were a few instances of hypernatraemia in the first week caused by high insensible water loss. There were high levels of sodium excretion up to 16% of filtered sodium, or 21 mmol/kg/day, in the first two postnatal weeks. Highest levels of sodium excretion were seen in the most immature infants in the first week. In most infants sodium excretion increased either in the first week or later before a subsequent decline. Potassium excretion was often high in the first week, as much as 96% of filtered potassium, or 5 mmol/kg/day, and is associated with early hyperkalaemia.


Renal function in sick very low birthweight infants: 4. Glucose excretion. Renal glucose excretion was measured on 239 occasions in a sample of 36 infants of 25.5-33 weeks' gestation, birth weight 720-2000 g, between the ages of 0.5 and 32 days. Glucose was invariably present in urine from the first day. Fractional glucose excretion varied widely from 0.1% to 90% of filtered glucose and glucose excretion rate was up to 15.5 mmol/kg/day and was higher in the most immature infants, especially below 28 weeks' gestation. The highest values were in association with hyperglycaemia between 5 and 15 days but there was no consistent plasma glucose threshold with frequent glucose spillage at normal blood glucose concentrations. There was some correlation with sodium excretion in the first week suggesting that in the absence of hyperglycaemia with a normal filtered glucose load, glucose excretion is caused by proximal tubular immaturity.


Simultaneous measurement of preductal and postductal oxygen saturation by pulse oximetry in hyaline membrane disease. Preductal and postductal oxygen saturation were compared in 20 ventilated preterm infants with hyaline membrane disease to establish the frequency of right to left shunting and to assess the accuracy of postductus arteriosus blood gas sampling. One hundred and thirty eight comparisons were made and the frequency of right to left shunting was 17% (95% confidence interval 12 to 25%). Shunting episodes with possible preductal hyperoxia occurred far less commonly on a maximum of 5% of occasions. The findings in infants under 1000 g and of 24-28 weeks' gestation were not significantly different from larger or more mature infants. Shunting occurred significantly more frequently in very ill infants who subsequently died as a result of respiratory disease.


Effect of patency of the ductus arteriosus on blood pressure in very preterm infants. Forty one preterm infants (birth weight < 1500 g) were studied by daily Doppler echocardiography for the first week of life to examine the effect of a haemodynamically significant ductus arteriosus (HSDA) on systemic blood pressure. Hourly records of blood pressure were averaged for each infant to produce a 24 hour mean value and the infants were then allocated to groups according to whether, by echocardiographic criteria, there was a HSDA on that day. In infants from 1000 to 1500 g the differences in all parameters of blood pressure between those with and without a HSDA were not significant. In infants < 1000 g the mean blood pressure was significantly less in the infants with a HSDA throughout the first week of life. Systolic blood pressure was reduced by as much as diastolic blood pressure and as a result the pulse pressure did not differ. Infants < 1000 g with a HSDA were given more plasma and a greater number received inotropic support. Gestational age, respiratory disease severity, and complication rates did not differ between those with and without a HSDA. The possibility of a clinically silent HSDA should be considered before large amounts of plasma volume expanders are given to treat hypotension in infants < 1000 g.


Annual audit of neonatal morbidity in preterm infants. Annual odds ratios, standardised for known confounding variables, were used to examine trends in major neonatal morbidities among 3220 preterm infants of less than 35 weeks' gestation admitted to a regional referral centre between 1980 and 1991. Despite improved survival, the risk of major cerebral haemorrhage, ventriculoperitoneal shunt insertion, and necrotising enterocolitis was unchanged. A recent reduction in risk of pneumothorax and persistence of the arterial duct was noted. An increased risk for chronic lung disease over time could be accounted for by increased survival, although a similar increase in risk for infection remained unexplained.


Prediction of neurodevelopmental outcome in the preterm infant: short latency cortical somatosensory evoked potentials compared with cranial ultrasound. One hundred and twenty six preterm infants, with a gestational age of 34 weeks or less, were studied to compare the predictive value of somatosensory evoked potentials (SEPs) with that of cranial ultrasound. A normal N1 latency was no guarantee of a normal outcome, nor did a persistently delayed N1 latency always correlate with a poor outcome. As a predictor of cerebral palsy, SEPs had a sensitivity of 44% and a specificity of 92%. The presence of a large haemorrhage (grade IIb/III) or cystic leukomalacia on cranial ultrasound predicted cerebral palsy with a sensitivity of 73.6% and a specificity of 83.1%. These results demonstrate that the role of SEPs recorded after median nerve stimulation is limited in preterm infants.


Membrane humidification--a new method for humidification of respiratory gases in ventilator treatment of neonates. A humidifier system for neonatology that functions according to the 'membrane humidification' principle was subjected to a performance test in our laboratory. Humidification and heating of the respiratory gases took place in a module consisting of a net of hollow fibres placed inside the incubator. In 18 measurement combinations flow, respiratory gas temperature, and incubator temperature were varied. At respiratory gas temperatures within the range of 33-37 degrees C the minimum international standard for the absolute air humidity in the respiratory gas was achieved or exceeded in all measurements. No controlled clinical tests regarding the importance and long term effects of different temperatures and different humidity levels in the inspiratory air are yet available for the ventilation treatment of neonates.


Randomised controlled trial of colloid infusions in hypotensive preterm infants. Colloid infusions are often given to treat hypotension in preterm infants. The aim of this work was to assess whether it was the amount of protein or the volume of the colloid infused which accounted for the observed increase in blood pressure. Sixty preterm infants were randomised (20 in each group) to receive 5 ml/kg 20% albumin, 15 ml/kg fresh frozen plasma, or 15 ml/kg 4.5% albumin. All infusions were given at a rate of 5 ml/kg/hour in addition to maintenance fluids. The infants were randomised when hypotensive (systolic blood pressure less than 40 mm Hg for two hours). There was no significant difference in the blood pressure of the three groups before or one hour after beginning the infusion. The mean increase in blood pressure one hour after completing the infusion, however, was significantly lower in infants receiving 20% albumin: 9% compared with 17% in the group receiving 4.5% albumin, and 19% in the group receiving fresh frozen plasma. It is concluded that the volume infused rather than albumin load is important in producing a sustained increase in blood pressure.


Cardiac tumours in intrauterine life.

Cardiac tumours in intrauterine life. Since 1980, 11 examples of cardiac tumour have been detected in the fetus out of a total of 794 congenital cardiac malformations. Patients were referred because of fetal hydrops in two, a family history of tuberous sclerosis in two, and because of the detection of a tumour mass during a scan at the local hospital in seven. The gestational age range at presentation was from 20-34 weeks. Of eight fetuses where death occurred, the histological type was rhabdomyoma in seven and teratoma in one. In seven cases, the lesion appeared single and in four there were multiple tumours. In two of the cases of rhabdomyoma, other family members had evidence of tuberous sclerosis. Termination of pregnancy took place in four cases; of seven continuing pregnancies, spontaneous intrauterine death occurred in four, and three children are still alive. Two of the three survivors has the clinical picture of tuberous sclerosis. The last case is as yet only 1 month old. In summary, even where the lesion is single, the most likely diagnosis in fetal cardiac tumour is rhabdomyoma, with associated tuberous sclerosis. However, the characteristic features of this latter condition may not become evident until some months after birth.


Changes in the plasma aminogram of parenterally fed infants treated with dexamethasone for bronchopulmonary dysplasia. A substantial increase in the plasma concentration of most amino acids was observed in 59 preterm infants with chronic lung disease soon after the initiation of dexamethasone therapy. The size of increase appeared to be dose related. This phenomenon is likely to be the result of steroid induced protein catabolism. Interestingly, neither phenylalanine nor tyrosine concentrations were significantly increased.


Coagulation screening tests in high risk neonates: a prospective cohort study. Forty seven infants in a prospective cohort of 170 high risk neonates without signs of overt bleeding had abnormal coagulation screening tests within 36 hours of birth. Early thrombocytopenia was a better predictor of prolonged prothrombin times and hypofibrinogenemia than very low birth weight, fetal growth retardation, or poor five minute Apgar scores.


Clinical application of urine antigen detection in early onset group B streptococcal disease. The aim of this study was to test the sensitivity and specificity of antigen detection for group B streptococcus (GBS) from the urine of neonates with early onset GBS sepsis. GBS sepsis was defined as early (< 48 hours) signs of sepsis in a neonate colonised with GBS. Neonates of 26 weeks' gestation or more, considered at risk for sepsis, were prospectively investigated for one year. Investigations included culture of superficial swabs to assess colonisation, blood culture, and the Wellcogen Strep B latex particle agglutination test on urine. Of 188 neonates investigated, 17 (9%) had GBS sepsis. The urine antigen test had a sensitivity of 88% and specificity of 98%. The positive predictive value was 79% and the negative predictive value 99%. Blood culture was positive in only five neonates (29%). The annual incidence of GBS sepsis was 4.0 per 1000 and of blood culture positive GBS disease was 1.2 per 1000 live births. Three neonates died. The application of the urine antigen test of clinical neonatal practice is discussed.


Recovery of intralipid from lumbar puncture after migration of saphenous vein catheter. A term female infant was admitted to the intensive care unit with the diagnosis of tetralogy of Fallot with critical pulmonary stenosis. On the seventh day of life a long saphenous line was inserted that remained without complications until seven days later when the infant appeared septic. A lumbar puncture demonstrated the presence of intra-lipid in the cerebrospinal fluid that we interpreted as due to migration of the saphenous catheter. The child had an uneventful recovery.


Meconium ileus in the absence of cystic fibrosis. Although meconium ileus in the absence of cystic fibrosis is considered a rare event, it was found that eight of 37 (21.6%) newborn infants with meconium ileus had no laboratory or clinical evidence of cystic fibrosis.


Validation of a portable indirect calorimetry system for measurement of energy expenditure in sick preterm infants. A portable indirect calorimeter adapted from adult use was validated for use in preterm infants. Oxygen consumption (VO2) and carbon dioxide production (VCO2) were subsequently measured in 16 preterm infants breathing spontaneously in room air (canopy mode) and in nine preterm infants receiving intermittent positive pressure ventilation (ventilator mode). Validation of the system was performed using a gas injection technique with nitrogen to simulate VO2 and carbon dioxide for VCO2. Mean errors in validation of the canopy mode were 1.4% and 0.2% for VO2 and VCO2 with limits of agreement of 0.6 (+2SD) ml/min and -1.3 (-2SD) ml/min, and 0.9 (+2SD) ml/min and -2.3 (-2SD) ml/min respectively. In validation of the ventilator mode mean errors were -1.8% and -5.05% for VO2 and VCO2 with limits of agreement of 1.02 (+2SD) ml/min and -0.74 (-2SD) ml/min, and 0.93 (+2SD) ml/min and -1.45 (-2SD) ml/min respectively. Values of VO2 and VCO2 in 16 preterm infants in the canopy mode were 6.2 ml/kg/min (0.5 1SD) and 6.7 ml/kg/min (0.6 1SD) and in nine preterm infants in the ventilator mode 4.98 ml/kg/min (1.09 1SD) and 4.74 ml/min/kg (1.08 1SD) respectively. Mean energy expenditure was 45.5 kcal (191 kJ)kg/day for infants measured in the canopy mode and 35.5 kcal (149 kJ)/kg/day for ventilated infants. This metabolic system can be adapted for use in the newborn but accuracy is reduced when it is used in those weighing less than 1000 g.


Fatal perinatal nephropathy with onset in intrauterine life. A girl, born at 29 weeks' gestation, died of renal failure aged 16 days. Postmortem histology showed diffuse mesangial sclerosis with failure of development of the cortex. This is an unusual cause of neonatal renal failure, and it demonstrates the effect of disease arising in utero and influencing the development of the kidney.


When will my baby go home?

When will my baby go home? The length of stay of preterm babies discharged from a neonatal nursery was determined and the predictive value of perinatal factors on the duration of stay was assessed on 762 preterm Salford born babies admitted to Hope Hospital neonatal unit between April 1986 and November 1990. The data were analysed using multiple logistical regression and forward stepwise regression analysis. Babies were discharged at a median (quartile range) postconceptional age of 36.3 (35.3-37.6) weeks. Seventeen factors were found to be strongly predictive of discharge date. The most significant predictive factor was gestational age accounting for 40% of variability compared with respiratory difficulties (6%), low birth weight (4%), sepsis (2%), and metabolic problems (1%). Most babies are discharged at approximately the same postconceptional age despite variations in their clinical course. Gestational age at birth is the most powerful predictive factor of time of discharge.


Intermittent ductal patency in healthy newborn infants: demonstration by colour Doppler flow mapping. Colour Doppler flow mapping was used to determine the time of closure of the arterial duct in 51 healthy newborn infants. Initial time of closure corresponded with previous reports: 20% on the first day, 82% by the second day, 96% by the third day, and 100% by the fourth day. Twenty infants were delivered by caesarean section and followed up for seven days even if the duct had apparently closed; in six intermittent patency was demonstrated with flow in the third, fourth or fifth day, although earlier functional closure had been observed. All were found to be closed on the sixth and seventh days. It is necessary to be aware of the phenomenon of intermittent closure in any study determining or assessing the effect of any intervention on ductal patency.


Neonatal meningococcal conjunctivitis associated with meningococcal meningitis. Two infants are described in whom identical strains of meningococcus were isolated from both the eyes and the cerebrospinal fluid. This suggests that the eye may be a portal of entry in at least some cases of perinatally acquired neonatal meningococcal disease and has important implications for the management of purulent conjunctivitis in the newborn.


Clinical, light and electron microscopic features of recessive ichthyosis congenita type III. The recessively inherited congenital ichthyoses have ultrastructural features which indicate abnormal epidermal lipid metabolism. The ultrastructural markers of the three recessive congenital ichthyosis groups are lipid droplets in horny layers (type I), cholesterol clefts (type II) and membrane structures (type III). We describe six patients from five families belonging to the last group. The variable clinical phenotype alone does not allow the delineation of this disease, but together with the ultrastructural characteristics the subtype is unequivocal. In addition to the membrane structures, half of the cases showed abnormal keratinosomes and vesicular complexes. Membrane-bound vacuoles and needle-like slits were exceptionally found. The onset of the ichthyosis was variable, in contrast to other patients described under the heading recessive congenital ichthyosis.


Further evidence that acanthosis nigricans maligna is linked to enhanced secretion by the tumour of transforming growth factor alpha. The pathogenesis of cutaneous paraneoplastic syndromes is still under discussion. Since many of these syndromes, including acanthosis nigricans, are proliferative skin disorders it is believed that products secreted by the tumour stimulate the keratinocytes to proliferate. Growth factors like transforming growth factor alpha (TGF-alpha) are known to be highly mitogenic for keratinocytes in vitro. Here we report on a patient with a poorly differentiated gastric cancer and a full clinical picture of acanthosis nigricans characterized by diffuse hyperkeratosis and multiple papillomatous lesions of the skin with involvement of the conjunctivae. In Southern blot analysis of the tumour tissue from this patient amplification of the epidermal growth factor (EGF) receptor, the common ligand for TGF-alpha and EGF, was shown. Immunohistochemically, prominent staining was found throughout the tumour using anti-TGF-alpha antibodies. In a series of 25 investigated gastric tumour biopsies, four tumours showed amplification of the EGF receptor and one additional biopsy was positive for TGF-alpha. Since there is no other report describing the link between TGF-alpha and acanthosis nigricans, except that of Ellis et al. 1987, we present a new case suggesting a possible link between growth factors and acanthosis nigricans maligna.


Increase in types IV and VI collagen in cherry haemangiomas. The capillaries in cherry haemangiomas show perivascular hyalinized sheaths. In order to clarify the nature of this sheath material, the extracellular matrix of cherry haemangiomas from 20 normal volunteers (age range 30-64 years) was investigated using immunohistochemical and electronmicroscopical methods. Antibodies against collagen types III, IV and VI and laminin were used. Hyaluronic acid was visualized using the hyaluronic acid binding region of the cartilage proteoglycan as ligand. Electronmicroscopically, the sheaths contained multilaminated basement membrane-like material, collagen fibres 20-25 nm thick with a periodicity of 67 nm and broad-banded aggregates with a periodicity of 100 nm (zebra bodies or fibrous long-spacing fibres). Immunohistochemically, type IV collagen was stained throughout the whole sheath material. Staining for laminin was more confined to the endothelial side of the sheath. Intense staining for type III collagen and hyaluronic acid was found in the connective tissue of the subpapillary layer and between the cherry haemangioma capillaries. Much weaker staining for type III collagen and no staining for hyaluronic acid were found invariably in an area 4-10 microns thick directly around the capillaries. Both sheath material and intercapillary connective tissue of the haemangiomas showed pronounced staining for collagen type VI. Immunogold staining revealed that type VI collagen was localized to microfibrils 5-6 nm thick and to the broad-banded aggregates with 100 nm periodicity. These findings further underline the assumption that the broad-banded aggregates consist of type VI collagen.


Immunochemical detection of unrepaired cyclobutane-type pyrimidine dimers of DNAs extracted from human skin tumours. Unrepaired cyclobutane-type pyrimidine dimers of DNA extracted from human skin tumours were examined by an immunoblotting method using polyclonal antibodies raised against UV-irradiated calf thymus DNA. A total of 40 DNA samples extracted from seven SCC lesions, two AK lesions, two lymphomas, one basal cell epithelioma, one eccrine poroma, one neurofibroma of Recklinghausen's disease, on verruca vulgaris, four femoral normal skins and white blood cells of 21 humans were studied by immunoblotting using this antibody. Two of the 40 DNAs examined, one from facial actinic keratosis (AK) and one from a squamous cell carcinoma (SCC) which developed form facial AK formed immunoprecipitates. It was found, using photoreactivation enzyme plus visible light, that both immunoprecipitates were cyclobutane-type pyrimidine dimers. In addition, immunofluorescent studies on AK tissue were positive in an immunoblotting assay and revealed that the unremoved photodamage in DNA remained in the nucleus of AK cells. These findings indicate that these tumour cells may be deficient in the enzyme function for repairing photoproduct damage. The unrepaired cyclobutane-type pyrimidine dimer in AK cells might reflect the genetic process in multistage carcinogenesis as well as in xeroderma pigmentosum.


Effects of cepharanthine and minoxidil on proliferation, differentiation and keratinization of cultured cells from the murine hair apparatus. The effects of cepharanthine and minoxidil on proliferation, differentiation and keratinization of cultured cells from the murine hair apparatus were examined electron microscopically. Both cepharanthine and minoxidil stimulated cell proliferation and delayed initiation of differentiation and keratinization of the cultured cells. On day 6, most control cells (87%) cultured in a 0.03 mM calcium medium without cepharanthine and minoxidil were differentiated into several subpopulations corresponding to those of in vivo cell layers of the hair apparatus, while most of the cells cultured with cepharanthine (71%) or minoxidil (70%) were still immature. On day 13, the number of degenerated cells increased (63%) in the control culture, whereas in the culture treated with cepharanthine or minoxidil, cell degeneration scarcely occurred (5% and 8%, respectively). Differentiated cells having tonofilaments were often observed in the cepharanthine- and minoxidil-treated cultures (76% and 72%, respectively). Elevation of extracellular calcium up to 1.0 mM induced keratinization (34%) in the control culture on day 6, while no keratinized cells were observed in the cepharanthine- or minoxidil-treated culture. On day 13 keratinization similarly occurred in the cultures with cepharanthine (30%) or minoxidil (48%). These results show that both cepharanthine and minoxidil may directly influence proliferation, differentiation and keratinization of cultured cells from the hair apparatus.


A murine in vitro model of allergic contact dermatitis to sesquiterpene alpha-methylene-gamma-butyrolactones. The use of a lymphocyte transformation test (LTT) to provide evidence of allergic contact dermatitis was investigated. The haptens studied were alantolactone and isoalantolactone, two moderate allergens from Inula helenium L., a decorative and medicinal plant. Only alantolactone showed a significant response in vivo and in vitro in mice sensitized epicutaneously, without using Freund's complete adjuvant. Isoalantolactone did not show any sensitizing capacity in the murine model studied. The comparison of in vitro lymphocyte proliferation and in vivo allergenic capacity showed a good correlation and clearly demonstrates that, of the two sesquiterpene lactones, alantolactone is the better sensitizer.


Ultrastructural changes in Dunaliella minuta following acute and chronic exposure to copper and cadmium. The ultrastructural changes taking place after short-term acute exposure to copper, cadmium and a combination of the two metals were examined. Additionally, the effects of long-term (8 months) exposure to ambient concentrations of these metals were investigated. Exposure to 0.34 microM cadmium affected the photosynthetic potential of this alga, by reducing the relative volume of the chloroplast by 23.27%. It also led to 74.6% increase in the relative volume of starch granules. Cells challenged with 0.34 microM cadmium and 7.57 microM copper had 33.49% larger volumes than controls, and their relative lipid volumes increased by 170%. In contrast, the relative volume of their pyrenoids decreased by 41.46%. Similar results were obtained after chronic exposure to 4.9 x 10(-4) microM copper with the relative volume of the pyrenoid being 28% smaller than the controls.


Heavy metal and selenium concentrations in black skimmers (Rynchops niger): gender differences. Most studies of heavy metals and selenium have not examined or have failed to find differences in concentrations in the tissues of birds as a function of size or sex. Heavy metal and selenium concentrations were analyzed in breast feathers of adult black skimmers Rynchops niger, a species with marked sexual size dimorphism in which males average 35% heavier than females. Females had significantly higher concentrations of lead and cadmium than males, but there were no gender differences in mercury, selenium, chromium, manganese, and copper despite the marked sexual dimorphism in body size. There were no significant correlations of bird weight or wing length and metal and selenium concentrations, and few correlations among metal and selenium concentrations in the feathers.


Heavy metal and selenium levels in young cattle egrets from nesting colonies in the northeastern United States, Puerto Rico, and Egypt. Colonially-nesting species of herons and egrets breed mainly in coastal areas, along rivers or near other large bodies of water. Such areas are also preferred for human development, exposing nesting birds to various pollutants. From 1989-1991, the concentrations of heavy metals and selenium were studied in the feathers of fledgling cattle egrets Bubulcus ibis, a terrestrially-feeding insectivore, from New York and Delaware in the northeastern United States, from Puerto Rico, and from Egypt. There were geographic differences in the concentrations of lead, mercury, cadmium, manganese, selenium, and chromium in the feathers of these egrets. Lead levels were 41 times higher in the feathers of cattle egrets from Cairo compared to the other sites. This difference was attributed to the continuing use of leaded gasoline and the dense automobile traffic in Cairo. However, other differences remain unexplained. Similarly, levels of chromium and manganese were also higher in Cairo than at any other sites. Cadmium levels were similar at all places except for higher levels in eastern Puerto Rico. Mercury concentrations were twelve times higher in the feathers of cattle egrets at Aswan compared to Cairo. In Puerto Rico, we also compared levels in adult cattle egrets with young and found higher concentrations of mercury and manganese, but lower concentrations of selenium in the adults. Using feathers from young cattle egrets is a potentially sensitive tool for biomonitoring for metals, especially lead, since they reflect the local area surrounding the breeding colony.


Subchronic toxicity and reproduction effects of tri-n-butyltin oxide in Japanese quail. A subchronic toxicity/reproduction study was performed in Japanese quails that were fed a diet containing 0, 24, 60, and 150 mg tri-n-butyltin oxide (TBTO) per kg basal diet for 6 weeks. Eggs produced during the 6 weeks of treatment were incubated and hatched, and chicks hatched from eggs collected in weeks 5 and 6 of exposure were reared for 2 weeks. In parent quail, neither diminished food consumption nor any overt toxic or histopathologic signs were observed following exposure to TBTO. A statistically significant decrease in hatch-ability and increase in percent of chicks found dead in the shell were observed following TBTO exposure at concentrations of 60 and 150 mg/kg food. However, no significant, adverse effects were recorded on total egg production, eggshell thickness and cracked eggs. Blood chemistry parameters of birds measured at the last day of TBTO treatment revealed a statistically significant decrease in serum aspartate aminotransferase (ASAT) enzyme activity among both sexes in all treatment groups. In addition, a statistically significant dose-related decrease in serum calcium level was observed in females only, while serum follicle stimulating hormone (FSH) levels were statistically significantly reduced in male birds in all treatment groups (approximately 50% of the controls). Moreover, a significant decrease in hepatic microsomal 7-ethoxyresorufin (EROD) activity was recorded in females fed 24 and 60 mg TBTO/kg diet and males fed 60 and 150 mg TBTO/kg diet, whereas pentoxyresorufin-o-deetylase (PROD) activity was only significantly decreased in males fed 150 mg TBTO/kg diet.(ABSTRACT TRUNCATED AT 250 WORDS)


Hydrolysis of ochratoxin A by the microbial activity of digesta in the gastrointestinal tract of rats. This study established the influence of dietary neomycin sulphate on the rate of hydrolysis of ochratoxin A (OA) by digesta from the intestine, and its effect on the excretion of OA and its hydrolyzed metabolite, alpha ochratoxin (O alpha), in the urine and feces of the rat. The first in vitro study demonstrated that digesta from the cecum and the large intestine were able to hydrolyze OA whereas digesta from the small intestine and stomach had very low hydrolytic activity against this substrate. Homogenates of the liver had no hydrolytic activity. The second in vivo study demonstrated that digesta from the large intestine and cecum of the neomycin treated rats was much less effective (P < 0.001) in promoting the hydrolysis of OA than digesta from the control rats. Neomycin when added directly to the in vitro system, however, did not affect the rate at which OA was hydrolyzed. In a third study, OA was administered in vivo to control and neomycin-treated rats. Rats fed the neomycin containing diet compared to those fed the control diet had a higher concentration (P < 0.005) of blood OA, and a greater cumulative excretion of OA plus O alpha over the entire 5 day collection period in the feces (P < 0.0001) and a corresponding decrease in the cumulative excretion of OA plus O alpha in the urine (P < 0.0001). Individually, there was a marked increase in cumulative fecal excretion of OA (P < 0.05) and a corresponding decrease in excretion of O alpha (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)


Disposition, behavior, and toxicity of methylcyclopentadienyl manganese tricarbonyl in the mouse. The disposition and toxicity of methylcyclopentadienyl manganese tricarbonyl (MMT), a potential substitute for lead in gasoline, was studied to investigate the different adverse effects in ddY mice after chronic oral administration at 0.5 g/kg in food for 12 months. There was no significant difference in intake between the control mice and the mice exposed to MMT (MMT group), but those given MMT suppressed weight significantly. The manganese content in the organs of the MMT group was 4.4-1.5 times significantly higher than that of the control group. In the MMT group, the manganese content was highest in the kidney, followed by the liver, thyroid gland, sublingual gland, and prostate gland. The blood manganese level in the MMT group was about 8 times higher than that in the control group. The urinary excretion of manganese in the MMT group was 5.4% of the daily oral intake. The organometallic form of the manganese involved is apparently absorbed more readily than inorganic forms. The stronger toxicity of MMT to the tissue than that of inorganic manganese is attributed to the significantly higher blood and tissue levels of manganese in the MMT group.


Temporal scales in ecological risk assessment. The process of human health risk assessment (HRA) was formalized in 1983 by the National Research Council to include hazard identification, dose-response analyses, exposure assessment and risk characterization. Risk assessment for ecologic endpoints is emerging as a new discipline. Although environmental impact statements have been conducted for many years, ecologists, managers and policy makers are beginning to formalize the process in terms of risk, and are adapting the HRA paradigm to ecological risk assessment (ERA). In this paper it is suggested that the temporal scales of the two processes differ, and that these differences should be incorporated in ecological risk assessment. Even when HRA techniques are applied to a single non-human species there are temporal variations including: (1) different and often variable life spans, (2) unpredictable lengths of lifestages and different metamorphic stages, and (3) indeterminate growth in some species. When these differences are considered for multispecies assemblages, the impact on the food web will result in exposures of differing magnitudes affecting different species. The challenges for ERA include developing general principles for estimating or predicting exposure to critical life stages of the dominant species in an ecosystem, and establishing the appropriate temporal scales for predicting impacts or evaluating outcomes.


Aircraft noise annoyance and average versus maximum noise levels. A questionnaire study was performed in seven areas located around the airports of Landvetter and Save, Gothenburg, in an attempt to elucidate the extent of annoyance in populations exposed to aircraft noise. Noise exposure was estimated as the energy equivalent level (Aircraft Noise Level--FBN) or as the number of aircraft with levels that exceeded 70 dBA, combined with the maximum noise level. The results were compared with data obtained from the earlier Scandinavian Aircraft Noise Investigation. The results supported the conclusion that the annoyance reaction is better related to the number of aircraft and the maximum noise level than to energy equivalent levels for noise exposure.


Bone lead measurements in patients with chronic renal disease studied over time. Results of longitudinal studies that involved the measurement of lead by different methodologies are presented for two groups of patients with chronic renal disease. Methodologies for all patients included x-ray fluorescence measurements of finger-bone lead. These measurements were conducted 5 y apart for one group of patients (n = 15). Initial measurements for the other group (n = 15) were supplemented by bone lead levels obtained either from skull at craniotomy or from skull, and sometimes rib, at autopsy. Most subjects also underwent ethylenediaminetetraacetic acid (specifically CaNa2 EDTA) lead-mobilization testing. A correlation between rate of decrease in finger-bone lead and immunoreactive parathormone levels was suggested. Renal patients were compared with age-matched controls, and their bone half-lives did not differ. The data are discussed and related to other results obtained from clinical and nonclinical populations in which trabecular and cortical bones were studied, and our results were consistent with evidence that more rapid turnover of lead occurs in trabecular bone than in cortical bone. No support was found for the hypothesis that patients who undergo renal dialysis accumulate lead in bone.


Effect of low-level body burdens of lead on the mental development of children: limitations of meta-analysis in a review of longitudinal data. The effect of low-level body burdens of lead on the intelligence of children, as measured by intelligence quotient (IQ), was assessed. We reviewed 35 reports from five longitudinal studies conducted in the United States and Australia. In each of these studies, infants were followed for 58 mo or less. The study populations consisted of low- and middle-socioeconomic-class infants who had low-level exposure to environmental lead. Blood-lead levels were measured in a standard fashion at various times, beginning in the prenatal period, and intelligence was first measured at 6 mo of age and was followed by subsequent assessments. Studies were assessed for quality by a review panel blinded to the identity of the investigators and their affiliations. Efforts were made to pool the data with meta-analytic techniques, but efforts were unsuccessful because the methods used to analyze and report data were inconsistent. Inconsistencies were as follows: (a) there were few instances in which IQ and blood-lead levels were measured at comparable times in different studies; (b) incompatibilities existed among the studies, including differences in independent variables, data transformations, and statistical parameters reported; (c) results conflicted when measurement intervals were comparable (i.e., heterogeneity); (d) patterns of regression and correlation coefficients were inconsistent; and (e) data were insufficient to interconvert the parameters reported. Consequently, definitive conclusions regarding the effect of low-level body burdens of lead on IQ could not be determined from the longitudinal data. Examination of the weight of the evidence from this and other studies, however, suggests an adverse relationship of lead on the intelligence of children.


Impact of environmental cadmium pollution on cadmium exposure and body burden. The body burden of cadmium, as estimated from 24-h urine cadmium levels, was determined in 1,523 subjects who were not occupationally exposed and who lived in five areas of Belgium. Urinary cadmium levels differed significantly with place of residence. These differences persisted after standardization for the other significant determinants (i.e., age, body mass index, smoking habits, social class, alcohol consumption, and menopause). The highest 24-h urine cadmium levels were found in subjects who lived in areas that contained cadmium-polluted soils. The body burden overload has been attributed mainly to the consumption of locally grown vegetables and the use of contaminated well water for cooking and drinking. Blood cadmium levels were also dependent on place of residence. However, the geographical differences in blood cadmium did not parallel those of urine cadmium. Blood cadmium is more influenced by recent exposure; therefore, this latter observation might reflect the recent implementation of preventive measures in some areas.


Decrease in blood cadmium levels over time in Belgium. During the time period from 1984 to 1988, blood cadmium concentration decreased by 56% in 31 males who were not occupationally exposed to cadmium and who lived in a Belgian urban area where there existed nonferrous industries. A 40% decrease in blood cadmium concentration was also observed in an independent cross-sectional survey conducted in 1985 and 1988 among 412 subjects who lived in a rural area. This latter decrease persisted when the main determinants of blood cadmium concentration--gender, age, and tobacco--were allowed for. The results presented are consistent with a decrease in environmental cadmium exposure in Belgium.


Exposure to environmental tobacco smoke in the household and urinary cotinine excretion, heavy metals retention, and lung function. The relationship between urinary levels of cotinine (U-cotinine) and arsenic (U-As), blood levels of cadmium (B-Cd), blood levels of lead (B-Pb), lung function, and questionnaire data on smoking habits were studied in 107 parents and their 46 children (7-10 y of age). There was a statistically significant relationship between the reported amount of tobacco smoked and U-cotinine levels. Nonsmokers who were married to persons who smoked had three times higher U-cotinine levels than nonsmokers whose spouses did not smoke. There was a significant association between the number of parents who smoked in the family and the U-cotinine levels of children. If only one parent smoked, maternal smoking was of greater importance than paternal smoking. There was also an association between U-cotinine and B-Cd. A study of lung function in the children revealed that vital capacity and functional residual capacity (corrected for sex, age, and height) increased as the number of parents who smoked increased. Therefore, the present study showed that (1) U-cotinine was a useful index of active smoking and environmental tobacco smoke exposure in adults and children, (2) U-cotinine was associated with the blood concentration of cadmium, and (3) environmental tobacco smoke exposure was associated with changes in lung function of children.


Respiratory health effects of alkali dust in residents near desiccated Old Wives Lake. Several years of drought have contributed to the desiccation of Old Wives Lake, a shallow, alkaline lake in southern Saskatchewan. The prevailing northwest wind, which blows across the 177-km2 dry lake bed, has generated airborne sodium sulfate, silt, and clay. Residents have reported nasal, eye, and respiratory irritation. A cross-sectional design that included 300 controls and 300 exposed subjects elucidated the potential adverse respiratory health effects of exposure to blowing alkali salt and dust. An increased prevalence of current cough, current wheeze, chronic cough, chronic wheeze, chronic eye irritation, and chronic nasal irritation was identified in the exposed population. Smoking-adjusted odds ratios were consistent with the prevalence ratios. Lung function did not differ between the exposed and the control populations. Rainfall during the study period reduced airborne dust levels and may have precluded demonstration of previously reported adverse effects.


[Stress urinary incontinence. Our results with the Burch's technique]. The aim of the surgical procedures utilized in the treatment of stress urinary incontinence (SUI) is to correct the posterior ureterovesical angle defect, thereby improving transmission of intraabdominal pressures to the urethra. We report our experience on 61 patients that had been diagnosed with SUI at our service from June 1984 to December 1990. Treatment was by the same operative procedure (Burch Technique) in all patients. The methods of exploration and the prognostic factors that might influence the outcome of the procedure are described. The short-term (3 months) success rate was 95%, the medium-term (1 year) 85.7% and the long-term (5 years) 77.1%. We underscore the convenience of prophylactic heparin therapy to prevent possible thromboembolic complications.


Lead acetate does not impair secretion of Sertoli cell function marker proteins in the adult Sprague Dawley rat. This study was conducted to determine the effects of lead on Sertoli cell function. Androgen binding protein and inhibin in testicular fluids and classical parameters of the hypothalamic-pituitary-gonadal axis were measured in adult male rats. For 10 wk, the rats were given water that contained 0.05%, 0.1%, 0.5%, and 1% lead acetate. Serum follicle-stimulating hormone, luteinizing hormone, and testosterone levels in all animals that ingested lead were normal at the middle and end of the experiment, as was the pituitary content of follicle-stimulating hormone and luteinizing hormone. Histologic examination revealed no disruption of spermatogenesis. Distribution of androgen binding protein in serum, seminiferous tubular fluid, and interstitial fluid was normal, as was the concentration of inhibin in interstitial fluid and seminiferous tubular fluid. However, a significant increase in epididymal androgen binding protein level and a decrease in seminal vesicle weight were observed in rats that ingested water containing 1% lead acetate. These results suggest that the effect of lead on spermatogenesis is not marked in adult Sprague Dawley rats, nor does Sertoli cell function appear to be affected adversely. Lead has been reported to alter in vitro metabolic function of Sertoli cells obtained from 16- to 21-d-old Sprague Dawley rats, and the Sertoli cells of juvenile animals may be more susceptible to lead than those of adult animals. The significant decrease in seminal vesicle weight and the abnormal epididymal androgen binding protein content indicate that lead could affect the male reproductive function in Sprague Dawley rats via its action on male accessory organs.


Nitrogen dioxide exposure and urinary excretion of hydroxyproline and desmosine. The relationship between average and peak personal exposure to nitrogen dioxide and urinary excretion of hydroxyproline and desmosine was investigated in a population of preschool children and their mothers. Weekly average personal nitrogen dioxide exposures for subjects who resided in homes with one or more potential nitrogen dioxide source (e.g., a kerosene space heater, gas stove, or tobacco smoke) ranged between 16.3 and 50.6 ppb (30.6 and 95.1 micrograms/m3) for children and between 16.9 and 44.1 ppb (12.8 and 82.9 micrograms/m3) for mothers. In these individuals, the hydroxyproline-to-creatinine and desmosine-to-creatinine ratios were unrelated to personal nitrogen dioxide exposure--even though continuous monitoring documented home nitrogen dioxide concentration peaks of 100-475 ppb lasting up to 100 h in duration. Significantly higher hydroxyproline-to-creatinine and desmosine-to-creatinine ratios were observed in children, compared with mothers (p < .001 and .003, respectively).


[Spontaneous perirenal hematoma].

[Spontaneous perirenal hematoma]. We report 10 cases of spontaneous perirenal hematoma that had been treated from 1974 to 1992. Retroperitoneal hemorrhage was secondary to renal disease in 7 cases, perirenal in 2 and extrarenal in 1. The etiology of the condition is analyzed in detail and the diagnostic usefulness of the different radiologic examinations are discussed. Making a preoperative diagnosis permits a more adequate surgical strategy.


[Bladder tumors: false recurrences].

[Bladder tumors: false recurrences]. The use of the new cytostatics for prophylactic therapy of superficial bladder tumor recurrence has been associated with fibrino-necrotic ulcers and eosinophilic cystitis. We underscore the problems in making the differential diagnosis which sometimes present with true tumor necrosis. We describe the characteristic features of both pathological conditions which permit these to be recognized before endoscopic maneuvers are performed. Their presenting features and course are analyzed.


[Mitoxantrone (MTX) versus mitomycin C (MMC) in the ablative treatment of Ta, T1 superficial bladder tumors. Phase III, randomized prospective study]. A prospective randomized study was conducted to determine the ablation capacity of mitoxantrone in Ta-T1 superficial bladder tumors versus mitomycin C, a drug whose intravesical ablation properties are well-known. Fifty-seven patients comprised the study. The tumor was not completely resected when the patient underwent TUR. This residual tumor was used as control. The patients were treated with either 20 mg Mitoxantrone or 40 mg mitomycin C weekly for 8 weeks and two other instillations every 15 days in 50 ml saline solution. Response to therapy was evaluated between the 4th and 8th week and classified as complete response (CR), defined as no gross and microscopic evidence of residual tumor, or no response (NR) or therapeutic failure. CR was observed in 77.7% of the patients treated with mitomycin C and in 50% in those that had been treated with Mitoxantrone. Treatment was discontinued because of side effects in 15% of the patients treated with mitomycin C and in 63.4% of those who received Mitoxantrone. We can conclude from the results of the present study that Mitoxantrone is a useful agent for ablation therapy of superficial bladder tumors, although the high incidence of severe side effects warrants its limited use and at high dilutions.


[Incidence of tumor pathology in a consecutive series of 497 kidney transplants in 431 patients]. From 1975 to 1989, 497 kidneys were transplanted in 431 patients. In this series, 12 tumors were observed in 11 patients (2.7%). There was a prevalence of skin tumors over the other tumor types (33%). The mean time of tumor presentation was 49 months post-transplantation. We investigated the possible influence of immunosuppression on tumor presentation. In our series, immunosuppression therapy was modified in only one case (Kaposi's syndrome), and the initial dose was maintained in the remaining tumors. Of the 11 patients, 5 have died and the remaining 6 patients are alive with a mean follow-up of 34 months.


[Clinico-therapeutic classification of urinary lithiasis]. Urinary lithiasis is a millenary disease for which different classifications have been developed: clinical, etiopathogenic, crystallographic, etc. The introduction of endoscopic surgery and extracorporeal lithotripsy in the last decade has created the need for a clinicotherapeutic classification as manifested by Rocco, Griffith, Tisselius, and other authors. We have developed the CEP/LTS-X classification, which evaluates the stone characteristics (C) [location and form (L), size (T), consistency (S) and number (X)], the excretory tract (E) and the renal parenchyma (P), and permits classifying the urinary calculus as LTS renal calculus types I, II, III, IV; LTS ureteral calculus types I, II, III; and LTS vesical and ureteral calculi types I and II, with related general characteristics that permit indicating treatment for each type: in situ ESWL or complementary endourological techniques, endoscopic or open surgery, alone or in combination.


[Ureteral tamponade in the treatment of urinary fistula: our experience]. Surgical correction is the treatment of choice for urinary fistulas. However, there are circumstances that advise against the use of this approach, basically when patient general condition is poor or life expectancy short; i. e., in the presence of an underlying malignant pelvic disease. In these cases, urinary diversion by percutaneous nephrostomy will suffice, although sepsis or derangement of electrolyte balance may sometimes develop due to the fistulous defect. Occlusion of the pyelo-ureteric junction and percutaneous drainage is a solution that causes no major complications. Two patients who could not be submitted to conventional surgery were treated by the foregoing procedure. Both patients have been followed for more than two years. The first case was a male who had undergone abdominoperineal resection due to carcinoma of the sigmoid colon. He developed stress ulcers, pulmonary thromboembolism, sepsis, paralytic ileus and bilateral ureteral fistula. The second case was an insulin-dependent female diabetic who had previously received radiotherapy to the pelvis. She developed a large vesicocutaneous fistula and public osteomyelitis after drainage of an inguinal abscess. Patient tolerance was good and no major complications were observed. In our view this palliative procedure should be considered in the management of patients with urinary fistula whose life expectancy is short. Its application can be extended to patients with inoperable carcinoma of the bladder or prostate and important symptoms.


[Ureteral revascularization in kidney transplantation. Report of a case]. We present uretero-pyeloplasty as a new surgical approach to stricture of the pyelo-ureteric junction in the transplant recipient. The foregoing is more frequently found in kidneys that are placed in the inverted anatomic position. The surgical procedure is performed without difficulty and at the same time permits us to evidence the presence of a new ureteral revascularization from the recipient after the interruption of vascular supply of the donor kidney.


[Nephrectomy following treatment with ESWL of staghorn lithiasis complicated with urinoma]. We report on a female patient that had undergone extracorporeal shock wave lithotripsy for a staghorn stone. We describe the endourological maneuvers that were performed, but had failed to avoid nephrectomy due to renal fistula with urinoma.


[Normal echographic anatomy of the penis and the perineum]. Sonourethrography has recently become available for evaluating the urethra. To perform this procedure correctly, precise knowledge of the ultrasound anatomy of the penis and perineum is required. Sixty-one males were studied using the 7.5 Mhz ultrasound transducer. During sonographic evaluation the site where the suspensory ligament of the penis is attached must be identified routinely. The nothc of the compressor nudae muscle in the posterior bulbous urethra can be visualized occasionally. The origin of the membranous urethra and urogenital diaphragm can be identified upon visualizing the entire urethral bulb and the cavernous bulb muscle.


[Bilateral renal lymphoma].

[Bilateral renal lymphoma]. Lymphomas can present as a solid tumor mass in one or both kidneys or compromise renal function directly or indirectly. Lymphoma should be discarded before performing surgical excision of a rapidly growing renal mass, particularly if involvement is bilateral. Reducing the renal mass may lead to difficulty in instituting specific chemotherapy for this tumor type.


[Non-venereal sclerosing lymphangitis of the penis]. Non-venereal sclerosing lymphangitis of the penis is a rare condition that affects the distal lymphatics of this organ. It has been reported to be frequently associated with trauma to this area and, although it has a minimum inflammatory component, its etiology is unknown. A serpinginous nodular lesion in the sulcus coronarius penis may be observed by the patient. Because it is generally self-limiting, treatment is initially conservative and surgical excision is performed only if symptomatic lesions persist. The present study reports an additional case. The literature is reviewed and the possible etiopathogenic mechanisms and therapeutic alternatives are discussed.


[Bladder schistosomiasis: presentation of a new case]. We report a case of urinary schistosomiasis involving only the bladder and mimicking a transitional cell pseudotumor. We describe the clinical and pathological features and discuss the diagnosis, medical and surgical treatment of this disease entity whose incidence is slowly increasing in black immigrants of the Maresme area of Barcelona.


[Liposarcoma of spermatic cord. A rare urologic tumor]. Malignant paratesticular tumors are uncommon. Of these, liposarcoma of the spermatic cord constitutes a rare tumor type with a good prognosis. It has a high rate of survival over 5 years. Inguinal orchiectomy generally suffices, although patients should be followed closely since local recurrence is not uncommon. The present study briefly reviews the literature on spermatic cord liposarcoma and reports an additional case that was treated exclusively by radical orchiectomy. Four years postoperatively the patient continues to be tumor-free.


[Acute adrenal hemorrhage and contralateral renal adenocarcinoma]. We report a case of spontaneous retroperitoneal hematoma from rupture of the right adrenal in a patient with asymptomatic left renal adenocarcinoma that had been incidentally detected during evaluation to determine the cause of the retroperitoneal hematoma.


Radiological progression of osteoarthritis: an 11 year follow up study of the knee. A follow up study was carried out in 1990 on 169 well documented patients initially presenting with osteoarthritis of the hands or knees between 1975 and 1977. Radiographic change in the knee was used as the outcome measure. Sixty three subjects had paired knee radiographs a mean of 11 years apart and were 69 (range 52-87) years old at follow up. Thirty subjects were known to have died, 28 were untraceable, and 48 were traced but did not have paired films available. The films were read independently and blind to time sequence by two observers using five different radiological scoring methods. Most of the knees did not increase in Kellgren and Lawrence grade, with only 33% deteriorating over the time period. The results were similar when a subject was categorised by their worst knee. When a more sensitive global score on paired films was used 50% of knees showed a slight deterioration and 10% improved. Visual analogue pain scores remained unchanged. Those with knee pain at baseline had a greater chance of progressing, as did those with existing osteoarthritis in the contralateral knee. These results suggest that most patients with osteoarthritis attending rheumatology clinics do not deteriorate radiographically or symptomatically over an 11 year period. More work is needed in the selection and early detection of subjects with a poor prognosis and in focusing early intervention on this high risk group.


Radiographic patterns and associations of osteoarthritis of the hip. A number of patterns of osteoarthritis of the hip are described, though studies are conflicting with respect to the frequency of such patterns and their associations. Two hundred and eleven patients (133 women, 78 men; mean age 66 years, range 29-86) referred to hospital with osteoarthritis of the hip were studied. Involvement was unilateral in 108 (51%) and bilateral in 89 (42%); 14 (7%) had undergone arthroplasty and were presenting with osteoarthritis hips). Sixty one per cent of hips had severe, 28% moderate, and 11% mild changes (Kellgren grade). Superior pole migration occurred in 82% (46% superolateral, 25% intermediate, 11% superomedial), medial/axial migration occurred in only 8%, and in 10% the pattern was indeterminate. In bilateral osteoarthritis of the hip the pattern was generally symmetrical. Superomedial and medial/axial patterns were proportionately more common in women, whereas superlateral osteoarthritis predominated in men. No association was found between multiple clinical nodes, radiographic polyarticular interphalangeal or first carpometacarpal osteoarthritis and any migration pattern. Any interphalangeal osteoarthritis was negatively associated with medial migration. Only 40% of hips could be categorised as hypertrophic or atrophic; chondrocalcinosis at any site was associated with atrophic osteoarthritis; no associations were seen with Forestier's disease. This large survey confirms the association between chondrocalcinosis and atrophic osteoarthritis of the hip. Importantly it suggests that gender, rather than associated osteoarthritis at other sites, is a major determinant of the pattern of osteoarthritis of the hip.


Exercise induced release of von Willebrand factor: evidence for hypoxic reperfusion microvascular injury in rheumatoid arthritis. Experimental evidence suggests that rheumatoid synovitis may be perpetuated by the generation of reactive oxygen species during hypoxic reperfusion injury. The latter occurs because increased intra-articular pressure during exercise exceeds synovial capillary perfusion pressure, impairing blood flow. The object of this study was to establish a marker for and the mechanism of synovial hypoxic reperfusion injury. Von Willebrand factor (vWF) is only released from endothelial cells and platelets and is an in vivo and in vitro marker of endothelial injury. In vivo exercise induced changes in plasma vWF were therefore investigated in patients with rheumatoid arthritis (RA) compared with controls and in vitro vWF release by human umbilical vein endothelial cells subjected to hypoxia reperfusion. Pre-exercise plasma vWF levels were 1001 and 817 IU/l, increasing after exercise to 1658 and 845 IU/l in patients with RA and controls respectively. Von Willebrand factor release from human umbilical vein endothelial cells followed a biphasic pattern, occurring during both hypoxia and reperfusion. Hypoxia reperfusion induced vWF release by human umbilical vein endothelial cells in vitro suggests that exercise induced vWF release in patients with RA is best explained by synovial hypoxic reperfusion injury. This study supports evidence that generation of reactive oxygen species plays a principal part in synovial hypoxic reperfusion injury and suggests vWF as a useful marker of this phenomenon.


Relative contribution of contact and complement activation to inflammatory reactions in arthritic joints. Although both the complement and contact system are thought to contribute to the inflammatory reaction in arthritic joints, only activation of complement has so far been well established, whereas contact activation and its contribution to arthritis has not been systematically explored. Complement and contact activation were assessed in 71 patients with inflammatory arthropathies and 11 with osteoarthritis using sensitive assays for C3a, and C1-inhibitor (C1INH)-kallikrein and C1INH-factor XIIa complexes respectively. Increased plasma concentrations of kallikrein-and factor XIIa-C1INH complexes were found in two and seven of the 71 patients with inflammatory arthropathies, respectively, and in none of the patients with osteoarthritis. Increased synovial fluid concentrations of kallikrein and factor XIIa complexes occurred in 13 and 15 patients with inflammatory joint diseases respectively, and in two patients with osteoarthritis. Contact system parameters did not correlate with clinical symptoms, local activity, or neutrophil activation. In contrast, synovial fluid concentrations of C3a and C1INH-C1 complexes were increased in all patients and in 20 patients with inflammatory arthropathies respectively, and were higher in patients with a higher local activity score. Synovial fluid C3a correlated with parameters of neutrophil activation such as lactoferrin. Increased plasma concentrations of C3a and C1INH-C1 complexes occurred in 13 and 11 patients with inflammatory joint diseases, and in one and two patients with osteoarthritis respectively. Plasma concentrations of C3a correlated with the number of painful joints. Thus contact activation occurs only sporadically in patients with arthritis and contributes little if anything to the local inflammatory reaction and neutrophil activation. These latter events are significantly related to the extent of complement activation.


Keratan sulphate in rheumatoid arthritis, osteoarthritis, and inflammatory diseases. Serum concentrations of antigenic keratan sulphate determined by an enzyme linked immunosorbent assay (ELISA) with a monoclonal antibody were studied in patients with rheumatoid arthritis (RA), osteoarthritis, ankylosing spondylitis, other inflammatory diseases, and a large control group of women without arthritis. Mean keratan sulphate concentrations were low in 117 women with RA compared with 227 female control subjects matched for age drawn from a community survey. There were significant correlations between serum keratan sulphate concentrations in patients with RA and serum C reactive protein and the erythrocyte sedimentation rate. Serum keratan sulphate concentrations were also low in 29 men and women with ankylosing spondylitis and 29 patients with arthritis and high concentrations of C reactive protein. In 98 women undergoing an operation for benign breast disease there were decreases in serum keratan sulphate concentrations after the operation which correlated with doses in serum C reactive protein. No differences were found in keratan sulphate concentrations in 137 women with osteoarthritis compared with controls. Within the group with osteoarthritis there were no differences for the various joint groups and there was no obvious correlation with radiographic severity or progression. These findings suggest serum keratan sulphate is unlikely to be useful as a diagnostic marker in osteoarthritis or RA but indicate a role for inflammation in the regulation of cartilage loss.


Measurement of HLA class I expression in ankylosing spondylitis. The importance of HLA-B27 in the pathogenesis of ankylosing spondylitis is uncertain: current evidence favours a role for the B27 molecule itself. The possibility that quantitative differences in HLA-B27 expression may exist between patients with ankylosing spondylitis, family members, and control subjects positive for B27 was examined using appropriate monoclonal antibodies, flow cytometry, and a 'model lymphocyte' coated with a known number of mouse immunoglobulin binding sites. No differences were found between the groups. HLA-A2, examined for comparison, was expressed in greater amounts than HLA-B27, but each contributed only 10-20% of the total class I antigens. Homozygotes expressed twice the amount of antigen expressed by heterozygotes. Synovial lymphocytes expressed more class I antigens than peripheral lymphocytes.


Central nervous system systemic lupus erythematosus mimicking progressive multifocal leucoencephalopathy. The case is reported of a patient with central nervous system systemic lupus erythematosus (SLE) with features of progressive multifocal leucoencephalopathy (PML) seen clinically and by magnetic resonance imaging. A brain biopsy sample showed microinfarcts. The use of magnetic resonance imaging and IgG synthesis rates in evaluating central nervous system lupus, the co-occurrence of SLE and PML, and the differentiation of these entities by magnetic resonance imaging and by histology are considered.


Mixed connective tissue disease presenting as a left sided pleural effusion. Mixed connective tissue disease (MCTD) usually occurs in women aged 13-50 years. Pleural effusion is rarely the presenting feature of this disease. The case is reported here of a male patient with MCTD who presented at the age of 79 years with a left sided pleural effusion.


Scleromyxoedema with features of systemic sclerosis. The case is described of a patient with scleromyxoedema with features typical of systemic sclerosis. The features were so characteristic that the disease was misdiagnosed as systemic sclerosis. A brief review of the association of the two diseases is given.


Retrocalcaneal bursitis in juvenile chronic arthritis. Retrocalcaneal bursitis has been described in various adult rheumatic diseases and septic bursitis unrelated to previous bursal disease has been reported in children. The case is reported here of a girl with juvenile chronic arthritis who developed non-septic retrocalcaneal bursitis; the diagnosis was suggested by a combination of clinical and radiographic studies and was confirmed by ultrasonography.


The 'GALS' locomotor screen.

The 'GALS' locomotor screen. The locomotor system is complex and difficult to examine. A selective clinical process to detect important locomotor abnormalities and functional disability could prove valuable. A screen based on a tested 'minimal' history and examination system is described, together with a simple method of recording. The screen is fast and easy to perform. As well as providing a useful introduction to examination of the locomotor system, the screen includes objective observation of functional movements relevant to activities of daily living. Its inclusion in the undergraduate clerking repertoire could improve junior doctors' awareness and recognition of rheumatic disease and general disability. It could also provide a valuable screening test for use in general practice.


Continuing evolution in the approach to severe liver trauma. Surgical and radiologic techniques from computed tomography (CT) scanning and embolization to temporary gauze packing and mesh hepatorrhaphy have been developed to make the management of severe liver injuries more effective. Surgical approaches for severe liver trauma have been oriented to two major consequences of these injuries: hemorrhage and infection. Early attempts at hemorrhagic control found benefit only in temporary intrahepatic gauze packing. The subsequent recognition of complications after liver injury blamed the practice of packing, which then remained unused for more than 30 years. Yet more aggressive attempts at controlling hemorrhage without temporary packing failed to improve results. Temporary perihepatic gauze packing therefore has been reintroduced, but this is probably an imperfect solution. Mesh hepatorrhaphy may control bleeding without many of the adverse effects of packing. Fourteen patients are reported with severe liver injuries who have undergone mesh hepatorrhaphy, bringing the current reported experience with mesh hepatorrhaphy to 24, with a combined mortality rate of 37.5%. Thus far, it appears that only juxtacaval injuries fail to have their hemorrhage controlled with mesh hepatorrhaphy, but many believe that these injuries may be controlled by perihepatic packing. Prophylactic drainage of severe liver injuries is a concept for which there is little evidence of benefit. Furthermore, recent radiologic developments appear capable of draining those collections that do occasionally develop in the postoperative period. The ultimate challenge of liver transplantation for trauma has been attempted, but the experience is thus far very limited.


Tumor necrosis factor alpha inhibits hepatocyte mitochondrial respiration. Although direct cytotoxicity is a well-established phenomenon of tumor necrosis factor alpha (TNF alpha)-induced tissue damage, the intracellular events leading to cell death are still poorly understood. To study the cytotoxic effects of TNF alpha on normal parenchymal cells, rat hepatocytes were purified and incubated with various concentrations of TNF alpha. Mitochondrial respiration, total protein synthesis, and enzyme release were measured to assess metabolic performance and cell integrity. Treatment with TNF alpha suppressed mitochondrial respiration in a concentration-dependent fashion, resulting in a reduction of the activity of complex I of the respiratory chain to 67.0 +/- 3.5% of that of untreated hepatocytes by 2000 U/mL TNF alpha. Under these conditions protein synthesis and the release of intracellular enzymes were significantly increased. Both hepatocellular enzyme release and inhibition of mitochondrial respiration appear to be associated with the generation of reactive oxygen intermediates by the hepatocyte itself, because oxygen radical scavengers prevented these adverse effects of TNF alpha. Inhibition of protein synthesis by cycloheximide as well as addition of cyclic adenosine monophosphate synergistically enhanced the suppression of mitochondrial respiration by TNF alpha, resulting in complex I activity of 6.9 +/- 1.6% and 24.9 +/- 2.9% of that of untreated cells. These data indicate that inhibition of mitochondrial respiration is one of the mechanisms by which TNF alpha induces tissue injury.