Comparability of patients with ANCA-associated vasculitis enrolled in clinical trials or in observational cohorts.

OBJECTIVES: To analyse the differences between patients with granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA) entered into randomised clinical trials (RCTs) and those followed in large observational cohorts. METHODS: The main characteristics and outcomes of patients with generalised and/or severe GPA or MPA with a five-factor score ≥ 1 enrolled in the French Vasculitis Study Group (FVSG) or the US-Canadian-based Vasculitis Clinical Research Consortium cohorts were compared to those enrolled in one of 2 FVSG clinical RCTs (WEG91, WEGENT) or 3 European Vasculitis Society clinical trials (CYCLOPS, CYCAZAREM, IMPROVE). RESULTS: 657 patients (65.3% with GPA) in RCTs were compared to 437 in cohorts (90.6% with GPA). RCT patients were older at diagnosis than the cohort patients (56.6 ± 13.9 vs. 46.8 ± 17.3 years), had higher Birmingham vasculitis activity score (19.5 ± 9.1 vs. 16.9 ± 7.4), and more frequent kidney disease (84.0% vs. 54.9%) but fewer ear, nose, and throat symptoms (56.8% vs. 72.2%). At 56 months post-diagnosis, mortality and relapse rates, adjusted for age and renal function, were higher for patients with GPA in RCTs vs. cohorts (10.7% vs. 2.5% [p=0.001] and 22.5% vs. 15.6% [p=0.03], respectively) but similar for patients with MPA (6.2% vs. 6.6% [p=0.92] and 16.6% vs. 10.1% [p=0.39], respectively). CONCLUSIONS: Patients with GPA or MPA in RCTs and those in observational cohorts show important differences that should be remembered when interpreting results based on these study populations.

Reports of abnormal cervical cancer screening tests in systemic sclerosis.

OBJECTIVE: To assess the prevalence of abnormal cervical cancer screening (Pap tests) reported by women with SSc onset before the age of 50 yrs. METHODS: Female members of a Canadian multi-centre SSc cohort completed standardized assessments and were questioned regarding a history of an abnormal Pap test. Potential correlates examined included demographics, reproductive history, smoking, diffuse vs limited SSc type, immunosuppressant exposure and SSc duration. RESULTS: In the 320 women with SSc onset before the age of 50 yrs, the life-time prevalence of an abnormal Pap test (according to self-report) was 25.4% (95% CI CI 20.9, 30.4%). By comparison, self-reported prevalence of abnormal Pap tests among general population Canadian females was recently reported at 13.8% (95% CI 11.6, 16.4%). Women with diffuse SSc (n = 142), tended to have a higher prevalence of self-reported cervical dysplasia (31.7%) compared with those with limited disease (20.7%), but the CIs overlapped. A multivariate logistic regression found a significant positive association between self-reported abnormal Pap test and diffuse disease [odds ratio (OR) 1.87; 95% CI 1.01, 3.47]. An independent association of an abnormal Pap test with smoking (OR 2.43; 95% CI 1.23, 4.78) and with younger age at disease onset was also noted. CONCLUSIONS: We noted a high prevalence of abnormal Pap tests self-reported in our sample. Increased risk was seen among those with diffuse SSc, and also among smokers and those with a younger age at disease onset. Thus, it seems prudent to ensure that adequate attention is paid to cervical cancer screening for women with SSc.

Sensorineural hearing loss in systemic lupus erythematosus: case report and literature review.

OBJECTIVES: We present a case of systemic lupus erythematosus with symptomatic sensorineural hearing loss which was successfully treated with azathioprine, as assessed both clinically and radiologically. We also present a review of the relevant literature. CASE REPORT: A woman with systemic lupus erythematosus presented with sensorineural hearing loss, initially on the right and subsequently developing on the left over several months. An audiogram revealed profound neurosensory hearing loss bilaterally. The patient was treated with prednisone 60 mg daily and azathioprine 200 mg daily. An improvement on the left was noted on follow-up audiography as well as on magnetic resonance imaging of the internal auditory canals and surrounding structures. CONCLUSION: Sensorineural hearing loss has been described in autoimmune disorders but is rare. Aural symptoms have been described, with varying incidences (0-57.5 per cent), in systemic lupus erythematosus. However, symptomatic sensorineural hearing loss is rare in systemic lupus erythematosus. Prednisone appears essential when an immunological or vasculitic cause is found. The use of azathioprine should be considered, as well as follow-up with magnetic resonance imaging to detect improvement.

Evidence of immunosuppression by Demodex canis.

Three clinically normal beagles, 3 beagles with localized demodectic mange (LDM), and 3 beagles with generalized demodectic mange (GDM) were investigated simultaneously 1-3 and 4-6 weeks from the appearance of the clinical signs. Blood clinical examination and reactivity of peripheral lymphocytes to Con A and PHA were investigated in the first instance, and reactivity to Con A, PHA, and LPS in the second. Eight aliquots were used in each blastogenesis assay for each dog. All dogs were negative for rheumatoid factor. The results of blastogenesis showed that many observations were distributed non-normally, and that not all dogs in each group responded homogeneously. Comparison of blastogenesis results between dogs demands careful statistical analysis. Responses to mitogens were normal in all dogs at 1-3 weeks except for the LDM dogs that showed an increased response to PHA. Only the response to Con A was moderately inhibited in the LDM dogs at 4-6 weeks. All responses were severely depressed in the GDM dogs at 4-6 weeks. This means that immunosuppression follows rather than precedes the clinical manifestations of GDM, and implies that the phenomenon is induced by the parasite or the host's reaction to it.

Effect of host sex and litter on the population dynamics of Echinococcus granulosus in dogs.

Twenty-one Beagle dogs consisting of 10 males and 11 females and belonging to 3 litters were infected with 60,000 E. granulosus protoscolices each. They were killed on day 40, the parasites from their intestines recovered, and the number of worms, average number of proglottides per worm, average length per worm, percentage of worms with a uterine cavity, and percentage of egg-bearing worms were determined for each dog and analyzed per sex and litter. On average, the dogs had 1,253 +/- 339 worms (means +/- standard error) with 2.42 +/- 0.1 proglottides, were 1.59 +/- 0.07 mm long, and 25.6 +/- 4.8% of the worms presented a uterine cavity and 1.2 +/- 0.6% bore eggs. The number of worms exhibited a bimodal distribution with 19 dogs having less than or equal to 2,565 worms and 2 greater than or equal to 5,520 worms. Average number of proglottides also showed a bimodal distribution with 7 dogs having less than or equal to 2.1 proglottides per worm and 14 dogs having greater than or equal to 2.4 proglottides per worm. The parasites were significantly more numerous in females than in the males (1,964 +/- 573 vs. 681 +/- 202), had more proglottides (2.67 +/- 0.08 vs. 2.15 +/- 0.16), and were longer (1.72 +/- 0.07 vs. 1.44 +/- 0.11 mm). The percentages of parasites with a uterine cavity (27.8 +/- 5.9 vs. 23.2 +/- 8.1) or bearing eggs (1.0 +/- 0.5 vs. 1.5 +/- 1.8) were comparable in females and males.(ABSTRACT TRUNCATED AT 250 WORDS)

Isoelectric heterogeneity of human prorenin (inactive renin) in body fluids.

Using flat bed isoelectric focusing, inactive renins from various body fluids were compared. Normal plasma inactive renin demonstrated six consistent peaks at pH 4.98, 5.14, 5.29, 5.47, 5.63 and 5.91, the largest being 5.29, 5.47 and 5.63. The isoelectric pattern of ovarian follicular fluid inactive renin was similar, with slight shifts at major peaks to a higher pH. Pregnancy plasma had inactive renin patterns like normal human plasma as did pleural fluid, lymphocoele fluid and plasma from anephric humans. Amniotic fluid inactive renin showed a markedly different pattern with major peaks at pH 5.00, 5.16 and 5.30. Fetal plasma (cord blood) also showed differences with only four peaks at 5.24, 5.40, 5.58 and 5.83. We conclude that human prorenin isoelectric patterns are similar for plasma, ovarian and most tissue fluid prorenins, but different for fetal plasma and amniotic fluid suggesting that these forms of renin do not cross the placental barrier.

Afghanistan: demographic consequences of war, 1978-1987.

"In this paper, I attempt to analyse the effects of war on the size and age-sex structure of the Afghan population, and to estimate the size of the Afghan population in Afghanistan by age and sex for the years 1978-1987. In doing so, I try to estimate the number of persons killed during the war and examine the validity of the available estimates." The analysis is based on data from the 1979 census, a 1987 survey, and other sources.

Stability of imipenem and cilastatin sodium in total parenteral nutrient solution.

The chemical stability and compatibility of imipenem-cilastatin sodium (Primaxin) in two different total parenteral nutrient (TPN) solutions was determined. TPN solutions consisted of 4.25% and 5% amino acids with 25% and 35% dextrose, respectively. Imipenem-cilastatin sodium was constituted with 10 ml of sterile water and admixed with 90 ml of TPN solution for a final concentration of 5 mg/ml of each drug. The final solutions were assayed at times 0 (immediately after admixture), 15 min, 30 min, 1, 4, 8, and 24 hr by a stability-indicating high-performance liquid chromatographic assay. Concurrently, test TPN solutions were monitored for pH changes, color changes, and precipitate formation. The potential effect of imipenem-cilastatin sodium on the stability of amino acids and other TPN additives was not evaluated. Imipenem and cilastatin sodium was stable (greater than or equal to 90% recovered) in each TPN solution at 15 min. A significant (greater than or equal to 10%) and steady decrease of imipenem recovery occurred at subsequent sampling times. Cilastatin appeared more stable than imipenem in both TPN solutions. A physical color change from colorless to dark orange appeared in each TPN solution over the 24-hr study period. Imipenem-cilastatin sodium is stable for 15 min in the TPN solutions studied; however, until the stability of the amino acids can be determined, the antibiotic should be administered through a separate line or Y-site while the TPN infusion is interrupted.

Sterility of total parenteral nutrient solutions stored at room temperature for seven days.

The sterility of total parenteral nutrient (TPN) solutions stored at room temperature for up to seven days after preparation was studied. The study was conducted in two parts. In part 1, a positive control phase was conducted to validate that the filter set would capture bacteria or fungi in the TPN solutions. In part 2,300 unused TPN solutions were retrieved from patient-care areas within 24 hours of preparation. These solutions were randomized into three study groups of 24, 72, or 168 hours after preparation. Each TPN solution was filtered aseptically using an inline 0.22-micron filter. The filters were suspended in brain-heart infusion broth and incubated at 35 degrees C. Filters were visually evaluated for turbidity as an indicator of microbial contamination. Microbial growth was reported in 2 of 100 samples filtered 24 hours after preparation (group 1) and in 1 of 100 samples filtered 72 hours after preparation (group 2). No growth was detected in TPN solutions filtered 168 hours after preparation (group 3). Turbid samples were subcultured, and contaminants were identified as coagulase-negative Staphylococcus species and gram-positive bacilli in the group 1 samples and coagulase-negative Staphylococcus species in the group 2 samples. The difference in contamination rates among the three groups was not significant. TPN solutions may be stored after preparation at room temperature for an extended time (up to 168 hours) without increasing the risk to patient safety. However, at this institution, expiration dates are extended only to the time that supports practical recycling of standard TPN solutions (72 hours).

Stability of penicillins in total parenteral nutrient solution.

The stability of ticarcillin, mezlocillin, and piperacillin in total parenteral nutrient (TPN) solutions at concentrations commonly used in adults was determined. Each antibiotic was added separately to three different amino acids-dextrose TPN solutions in two concentrations: 10 and 20 mg/mL. Amino acids concentration ranged from 25 g/L to 50 g/L. Dextrose concentration ranged from 100 g/L to 350 g/L. Solutions were assayed for antibiotic concentration immediately after mixing (time 0) and at 4, 8, 24, and 48 hours by high-performance liquid chromatography. The effect of the added penicillins on the stability of amino acids and other TPN additives was not investigated. Mezlocillin and piperacillin 10 and 20 mg/mL exhibited stability in TPN solution at 24 hours. Ticarcillin was stable for 24 hours at a concentration of 10 mg/mL, but at 20 mg/mL it was unstable at all times tested. The three antibiotics demonstrated the same characteristic stability in all three TPN solutions, suggesting that the concentrations of dextrose and amino acids did not affect stability. Ticarcillin, mezlocillin, and piperacillin are stable for 24 hours in the TPN solutions studied.

Total parenteral nutrition catheter sepsis: impact of the team approach.

For a period of 32 months from the inception of the Parenteral and Enteral Nutrition (PEN) Team at the University of Michigan, the infection rate (IR) related to central venous catheters (CVCs) for total parenteral nutrition (TPN) was prospectively evaluated. Six hundred twenty-two catheters were placed in 377 patients for a total of 9,200 patient days. The length of CVC stay ranged from 2 to 108 days with a mean of 14.5. CVC longevity was longer on units where certification of nurses by the PEN team was mandatory (mean 20.4 days, IR 3.5%) vs comparable units which utilized informal instruction (mean 14.4 days, IR 3.5%). Twenty-two catheters led to patient sepsis for a rate of 3.5%, or 2.39 CVC-related infections per 1000 patient days. The preteam infection rate was 24.0%, as determined by a 6-month prospective study. Infection rates for CVCs used for TPN only and those used for parenteral nutrition (PN) plus blood products, antibiotics, and CVP measurements were identical, 3.5%. The team approach can effectively increase PN catheter longevity and reduce infection rates. Conservative cost accounting of best and worst case scenarios determined a range of $3,700 to $8,900 per episode of catheter sepsis.

Humoral immunity in the prepatent primary infection of dogs with Echinococcus granulosus.

Twenty-one parasite-naive dogs were infected with 60,000 protoscolices of Echinococcus granulosus. Transformation of peripheral lymphocytes was investigated before and 29 days after the infection, immunoglobulin concentration and anti-hydatid fluid protein (HFP) titers in serum and feces before and at 35 days of infection, skin reactivity to HFP at 36 days, and characteristics of the parasites at 40 days. The infection caused a significant depression of the spontaneous, lipopolysaccharide-stimulated, and purified protein derivative-stimulated blastogenesis. Responses to phytohemagglutinin were unchanged and reactivity to concanavalin A was enhanced with the infection. Only the concentrations of IgG and IgA in the serum and IgA in the feces increased significantly after infection. Fifteen (71%) dogs produced significant serum titers of anti-HFP hemagglutinins but copro-antibodies were detectable in only 3 dogs at minimum titers. Titers were abolished by treatment with 2-mercaptoethanol. The serum of 11 (52%) dogs transferred passive cutaneous anaphylaxis to guinea pigs but none transferred skin reactivity to pups or rabbits. Five and 1 (but not 0.2) micrograms of HFP caused skin reactivity in 4 parasite-naive dogs. Nineteen (90.5%) infected dogs reacted significantly to skin inoculation of 0.2 microgram of HFP at 0.5 hours and 13 (62%) at 6 hours. The 7 dogs with the highest anti-HFP serum titers or the greatest skin reactivity at 6 hours had significantly less mature or fewer tissue parasites, respectively, than the 7 dogs with the smallest responses. Since there was evidence that the specific immunity was still developing at the time of the study, these results indicate that immunological diagnosis of, and artificial immunization against, canine echinococcosis are feasible.

Cell-mediated immunity in the prepatent primary infection of dogs with Echinococcus granulosus.

Cell-mediated immunity was studied in 21 parasite-naive dogs by transformation of peripheral lymphocytes with phytohemagglutinin (PHA), concanavalin A (Con A), or hydatid fluid protein (HFP) at 29 days of a primary infection with Echinococcus granulosus, and by delayed cutaneous hypersensitivity to HFP at 36 days of the infection. Infection depressed significantly the ability of unstimulated cells to proliferate but enhanced the response to Con A. The lymphocytes of four dogs reacted to HFP significantly above the average, and one dog exhibited cutaneous reactivity to 0.2 micrograms of HFP. Five or 1 but not 0.2 micrograms of HFP produced non-specific skin reactions in parasite-naive dogs. The 7 dogs with the highest reactivity to PHA or Con A had significantly fewer parasites than the 7 less reactive dogs. The differences in other parasite characteristics were not significant in the 7 dogs with the greatest or smallest reactivities. Correlation tests showed an inverse correlation of PHA reactivity with establishment and maturation of parasites, of Con A reactivity with growth and maturation, and of HFP with maturation.

Myiasis in a turkey.

A case of cutaneous myiasis was reported in a 3.5-month-old turkey. The bird was invaded by a very large number of maggots on its posterior half. The maggots killed the bird and consumed all the flesh within 48 hours. Microscopic examination of the maggots revealed that they belonged to Lucilia sericata (a dipterous fly). The incidence of myiasis in birds was also discussed.

Home parenteral nutrition: a hospital-based program with commercial logistic support.

Since home parenteral nutrition was introduced in the 1970's, a number of medical centers have formed successful home parenteral nutrition programs which have reduced expenses to the patient and third party payers by 50 to 73% over in hospital costs. However, the cost of maintaining these programs for training and follow-up has largely been absorbed by the hospital as a nonreimbursable teaching expense. To offset the costs of our growing program in these times of budget "caps," we have established an agreement between our hospital and commercial home care company which provides for patient instruction and follow-up by the hospital parenteral and enteral nutrition team and logistic support by the home care company. We used the average cost of our first five patients to establish a fee schedule which the commercial company agreed to pay the hospital parenteral and enteral nutrition team for its services. This agreement reduces the number of nurses and pharmacists that the commercial company would otherwise have to hire for teaching and follow-up of home care patients, and supports the concept of regional care in medical centers where parenteral and enteral nutrition teams maintain quality control, continuity of care, and efficient teaching programs for patients requiring home parenteral nutrition.

Biotin deficiency in a patient with short bowel syndrome during home parenteral nutrition.

A 54-year-old woman with short bowel syndrome was supported with home parenteral nutrition. Six months after receiving 2200 kcal/day of balanced home parenteral nutrition without biotin, she developed biotin deficiency with complete hair loss, eczematous dermatitis, waxy pallor, lethargy, and hypersthesias . Blood and urine samples were collected prior to treatment. Serum zinc was 64 micrograms/dl (nl 50-150 micrograms/dl), and the triene/tetraene ratio was 0.068 (nl 0.4), thereby ruling out zinc and essential fatty acid deficiencies. Serum biotin was 332 pg/ml (nl 520 +/- 220 pg/ml), and urine biotin was 5.22 ng/mg of creatinine (nl 4.3-95 with a mean of 30.2 ng/mg creatinine). The same parenteral nutrition regimen was contained and oral biotin was administered (10 mg/day). After 3 wk, serum and urine biotin levels were 650 pg/ml and 35.6 ng/mg creatinine, respectively. New hair growth was evident and all of her other symptoms resolved. Intravenous biotin was then provided (5 mg/day) for a month after which serum and urine biotin levels were 1316 pg/ml and 178 ng/mg creatine, respectively. The patient has been subsequently maintained on an intravenous multivitamin product containing 60 micrograms biotin per daily dose and remains free of signs and symptoms of biotin deficiency.

Regional variations in the distribution of population and levels of urbanization in the Democratic Republic of Afghanistan 1979-80.

PIP: The Preliminary 1979-80 Population Census Data of Afghanistan were used to examine the following: the regional variations in the spatial distribution and density of population; the incidence of concentration of population; the regional variations in the degree and levels of urbanization; the regional variations in the concentration of urban population according to size class of urban centers; and the growth of urban population during 1972-73 to 1979-80. The extraordinary natural conditions of Afghanistan divide the country into 4 different geographical zones or regions and causes many essential natural, socioeconomic, and cultural differentials among the regions. The total population in 1979-80 was 15,540,030. Of this, 2,488,642 persons were Nomadics, 16% of the total population. Of the total settled population in Afghanistan nearly 85% was living in rural areas at the time of the census. Afghanistan is a sparsely populated country with a density of 20 persons/sq km. This low population density is because of the hazardous geographical conditions. Most of the country is either mountainous or suffers with desert conditions and temperature extremes. Only about 1/8 of the country's area is arable. Despite low arithmetical density, the physiological density (population arable land) and agricultural (rural population/arable land), densities for the country as a whole were substantially high, 165/sq ha and 138 persons/sq ha. The pattern of the distribution of the rural population followed the pattern of total population with the Northern Plains having the largest number of the country's rural population (34.3%), followed by Eastern Southern, Central, and Southern Western regions, but the pattern of distribution of the country's urban population was totally different. The Eastern Southern region possessed 50.3% of the total urban population. The Central region had only 3.7% of the urban population. Only 15% of the population lives in urban areas. In 1979 there were 63 urban centers. Only 1 primary city, Kabul, had a population above 500,000. 3 cities had populations above 100,000 but below 500,000. Over a period of 7 years, the urban population increased by 30.3% but only 2 new places were added to urban class, and they had a population of less than 5000. The growth of urban poulation was primariliy due to the increase in the population of the urban centers themselves rather than by the addition of new centers.^ieng

Pathogaenicity of Toxoplasma gondii oocysts to ponies.

Nine ponies were fed 100,000 infective Toxoplasma gondii oocysts and were given corticosteroid injections before and after feeding the T gondii oocysts. Titers to the Sabin-Feldman dye tests (1:2 to 1:16,384) developed within postinoculation days (PID) 7 to 21 and antibodies persisted to PID 133. Toxoplasma organisms were isolated from the tissues of 4 ponies (heart of 4, brain of 2, spinal cord of 3, diaphragm of 1, skeletal muscle of 1, liver of 1, kidneys of 1) killed between PID 36 and 63, but not from 5 ponies killed between PID 117 and 150. Seemingly, ponies are one of the more resistant species of animals to develop clinical toxoplasmosis.