UriSed as a screening tool for presumptive diagnosis of urinary tract infection.

BACKGROUND: Although a quantitative urine culture is essential for the final diagnosis of urinary tract infection, it is time-consuming and an expensive procedure. Effective screening tests would be a promising alternative to provide immediate results for the clinician and eliminate unnecessary culturing for most of the negative samples. The aim of this study was to evaluate the performance of an automated sediment analyzer (UriSed) as screening tool for presumptive diagnosis of urinary tract infection. METHODS: We studied 1379 fresh midstream clean-catch urine samples from children to elderly. All samples were submitted to automated sediment analysis (UriSed) and quantitative urine culture (CLED medium agar). RESULTS: The sediment analyzer detected leukocyturia and/or significant bacteriuria with sensitivity of 97%, specificity of 59%, positive predictive value of 27%, negative predictive value of 99%, and accuracy of 64% at cutoff values of bacteria count ≥12.6 elements/hpf and WBC ≥6 cells/hpf. These data suggest a potential 52% reduction of unnecessary urine cultures. CONCLUSION: The UriSed seems to be an efficient tool for screening UTI with high sensitivity and low rate of false-negative results.

Skin prick-test reactivity to aeroallergens and allergic symptoms in an urban population of central Italy: a longitudinal study.

BACKGROUND: Cross-sectional studies report an increasing prevalence of allergic diseases, such as rhinitis and asthma. Not thoroughly known, instead, is the natural history of allergic sensitization and the progress of the allergic disease-related symptoms. AIM: The purpose of this study was to evaluate longitudinally the skin reactivity for the most common aeroallergens and the allergic symptoms in an urban population living in Perugia, a town of central Italy with a low-level of air pollution exposure. METHODS: In the 1998-1999 period 788 subjects were tested for skin reactivity to a panel of aeroallergens and underwent the administration of a questionnaire. These same subjects were part of a cohort of 1200 subjects who participated in a previous epidemiological study performed in 1984-1985 using the same tools. Subjects were aged between 14 and 64 years at the time of the first survey. RESULTS: In the present survey 196 subjects (24.9%) had skin reactivity to at least one aeroallergen, while in the previous survey 143 subjects (18.1%) had skin prick-test reactivity. The increase of the skin reactivity between the two observations was highly significant (P<0.001) and was mainly observed in subjects <40-years old. The greatest increment in skin reactivity was seen to Dermatophagoides pteronyssinus (house dust mite) allergen. Data obtained from questionnaires showed that subjects who declared allergic symptoms increased from 341 (43.3%) to 380 (48.2%). However, the increase was significant (P<0.01) only in subjects who had a positive association between allergic symptoms and prick-test reactivity and was greater for rhino-conjunctivitis than for asthma-related symptoms. CONCLUSIONS: In a cohort of urban population of the centre of Italy, exposed to a low and stable level of air pollution, the sensitization to common aeroallergens increased with time, mostly in people <40-years of age. The greatest increment was found for indoor allergens such as Dermatophagoides pteronysimus. A significant increase in allergic symptoms, mainly related to rhino-conjunctivitis, was observed only in the presence of positive prick test.

Effect of treadmill gait on bone markers and bone mineral density of quadriplegic subjects.

Quadriplegic subjects present extensive muscle mass paralysis which is responsible for the dramatic decrease in bone mass, increasing the risk of bone fractures. There has been much effort to find an efficient treatment to prevent or reverse this significant bone loss. We used 21 male subjects, mean age 31.95 +/- 8.01 years, with chronic quadriplegia, between C4 and C8, to evaluate the effect of treadmill gait training using neuromuscular electrical stimulation, with 30-50% weight relief, on bone mass, comparing individual dual-energy X-ray absorptiometry responses and biochemical markers of bone metabolism. Subjects were divided into gait (N = 11) and control (N = 10) groups. The gait group underwent gait training for 6 months, twice a week, for 20 min, while the control group did not perform gait. Bone mineral density (BMD) of lumbar spine, femoral neck, trochanteric area, and total femur, and biochemical markers (osteocalcin, bone alkaline phosphatase, pyridinoline, and deoxypyridinoline) were measured at the beginning of the study and 6 months later. In the gait group, 81.8% of the subjects presented a significant increase in bone formation and 66.7% also presented a significant decrease of bone resorption markers, whereas 30% of the controls did not present any change in markers and 20% presented an increase in bone formation. Marker results did not always agree with BMD data. Indeed, many individuals with increased bone formation presented a decrease in BMD. Most individuals in the gait group presented an increase in bone formation markers and a decrease in bone resorption markers, suggesting that gait training, even with 30-50% body weight support, was efficient in improving the bone mass of chronic quadriplegics.

Effect of treadmill gait on bone markers and bone mineral density of quadriplegic subjects

Quadriplegic subjects present extensive muscle mass paralysis which is responsible for the dramatic decrease in bone mass, increasing the risk of bone fractures. There has been much effort to find an efficient treatment to prevent or reverse this significant bone loss. We used 21 male subjects, mean age 31.95 ± 8.01 years, with chronic quadriplegia, between C4 and C8, to evaluate the effect of treadmill gait training using neuromuscular electrical stimulation, with 30-50 percent weight relief, on bone mass, comparing individual dual-energy X-ray absorptiometry responses and biochemical markers of bone metabolism. Subjects were divided into gait (N = 11) and control (N = 10) groups. The gait group underwent gait training for 6 months, twice a week, for 20 min, while the control group did not perform gait. Bone mineral density (BMD) of lumbar spine, femoral neck, trochanteric area, and total femur, and biochemical markers (osteocalcin, bone alkaline phosphatase, pyridinoline, and deoxypyridinoline) were measured at the beginning of the study and 6 months later. In the gait group, 81.8 percent of the subjects presented a significant increase in bone formation and 66.7 percent also presented a significant decrease of bone resorption markers, whereas 30 percent of the controls did not present any change in markers and 20 percent presented an increase in bone formation. Marker results did not always agree with BMD data. Indeed, many individuals with increased bone formation presented a decrease in BMD. Most individuals in the gait group presented an increase in bone formation markers and a decrease in bone resorption markers, suggesting that gait training, even with 30-50 percent body weight support, was efficient in improving the bone mass of chronic quadriplegics.

Urinálise: comparação entre microscopia óptica e citometria de fluxo / Urinalysis: comparison between microscopic and flow cytometry analysis

INTRODUÇÃO E OBJETIVO: O exame de urina é um procedimento de alta demanda, trabalhoso e pouco padronizado. Este estudo teve por objetivo avaliar o desempenho de um citômetro de fluxo na realização do exame de urina de rotina. CASUíSTICA E MÉTODOS: Foram analisadas 1.140 amostras de urina através de microscopia óptica comum e de citometria de fluxo (UF-100/SYSMEX). A precisão foi estabelecida com a análise de quatro amostras de urina (20 replicações cada). O cálculo da reprodutibilidade foi realizado a partir de 30 determinações de dois controles comerciais em dias consecutivos. RESULTADOS: As contagens de hemácias e leucócitos mostraram concordância de 91 por cento e 93 por cento, respectivamente. Cilindros, células e bactérias mostraram sobreposição dos valores fornecidos pelo UF-100 quando comparados com os relatados na análise microscópica. A precisão do UF-100 variou de 4 por cento a 155 por cento, com reprodutibilidade de 3 por cento e 25 por cento, dependendo do parâmetro avaliado. CONCLUSÃO: O equipamento UF-100/SYSMEX demonstra boa precisão, reprodutibilidade e concordância com a microscopia óptica. A utilização da citometria de fluxo implica numa maior agilização e padronização da rotina, bem como em uma nova maneira de reportar e interpretar o exame de urina de rotina.

INTRODUCTION: Urinalysis is a high demand procedure, with large amount of manual labor and poorly standardized. The purpose of this investigation was to analyze the performance of an automated system based on flow cytometry for routine urinalysis. MATERIAL AND METHODS: We analyzed 1,140 urine samples by light field microscopy and by flow cytometry (UF-100/SYSMEX). For the precision study of the UF-100, we calculated the within-run and between-run coefficients of variation using two different levels of commercial controls and four different urine samples. RESULTS: Erythrocytes and leukocytes counts by the two methods showed an agreement of 91 percent and 93 percent, respectively. Casts, epithelial cells and bacteria counts by the UF-100 showed a significant overlap when compared to microscopic analysis. Intra assay precision (within-run) ranged from 4 percent to 155 percent and interassay precision (between-run) varied from 3 percent to 25 percent, depending on the considered parameter. CONCLUSION: Flow cytometry is a precise and reproducible technique, with a strong correlation with the results obtained by microscopic analysis. Flow cytometry allows a better workflow and a new manner of reporting and interpreting routine urinalysis.

Sleep-disordered breathing in nonobese diabetic subjects with autonomic neuropathy.

To assess the occurrence and nature of sleep-disordered breathing (SDB) in 26 adult, nonobese diabetics (18 with autonomic neuropathy (DAN+) (age 45 (41-50) yrs; body mass index (BMI) 24.1 (22-26) kg x m(-2)) and eight without autonomic neuropathy (DAN-) (age 45 (35-55) yrs; BMI 24.8 (23-26) kg x m(-2))) overnight full sleep studies and measurements of central and peripheral carbon dioxide (CO2) chemosensitivity were performed. DAN+ were divided in two subgroups, according to the presence (DAN+PH+; n=10) or absence (DAN+PH-; n=8) of postural hypotension. Ten normal subjects were studied as controls (age 42 (36-48) yrs; BMI 24.4 (23-25) kg x m(-2)). In contrast to DAN- and controls, who did not show SDB, five DAN+ (four DAN+PH- and one DAN+PH+) had an apnoea/hypopnoea index > or = 10 and four DAN+ (two DAN+PH- and two DAN+PH+) had an apnoea index > or = 5. All the events were obstructive, occurring mainly during rapid eye movement (REM) sleep. Ten DAN+ exhibited a mean lowest oxygen saturation < 90% during REM sleep. No periodic breathing or central sleep apnoeas were found in DAN+PH+, although they had an enhanced central chemoresponsiveness to CO2. Both DAN+ subgroups showed a marked reduction in peripheral CO2 chemosensitivity. In conclusion, adult nonobese diabetics with autonomic neuropathy, independent of the severity of their dysautonomy, have obstructive sleep apnoea/hypopnoea with a frequency > 30%. A decrease in peripheral carbon dioxide chemosensitivity prevents adult nonobese diabetics with autonomic neuropathy and postural hypotension from experiencing posthyperventilatory central sleep apnoea, despite an increased hypercapnic central drive.

Accuracy of the urinary albumin to creatinine ratio as a predictor of albuminuria in adults with sickle cell disease.

AIM: To test the usefulness of a random urine specimen albumin to creatinine ratio (A/C) in predicting 12 hour urinary albumin excretion (12UA) in patients with sickle cell disease. METHODS: 12UA and A/C were measured in nocturnal urine collections and random morning urine samples, respectively, of 72 patients with sickle cell disease. RESULTS: The correlation of A/C values with 12UA values did not provide support for the use of random urine specimens for predicting urinary albumin excretion (UAE) in these patients. However, values of A/C >/= 0.45 and < 0.45 were indicative of raised and normal UAE, respectively. The sensitivity, specificity, and accuracy of the test were 100.0%, 87.2%, and 91.7%, respectively. CONCLUSIONS: This method cannot be recommended for predicting 12UA in patients with sickle cell disease, but it is useful for selecting patients who should collect 12 hour urine for the estimation of UAE.

Diagnostic investigation of ventilator-associated pneumonia using bronchoalveolar lavage: comparative study with a postmortem lung biopsy

The purpose of the present study was to validate the quantitative culture and cellularity of bronchoalveolar lavage (BAL) for the diagnosis of ventilator-associated pneumonia (VAP). A prospective validation test trial was carried out between 1992 and 1997 in a general adult intensive care unit of a teaching hospital. Thirty-seven patients on mechanical ventilation with suspected VAP who died at most three days after a BAL diagnostic procedure were submitted to a postmortem lung biopsy. BAL effluent was submitted to Gram staining, quantitative culture and cellularity count. Postmortem lung tissue quantitative culture and histopathological findings were considered to be the gold standard exams for VAP diagnosis. According to these criteria, 20 patients (54 percent) were diagnosed as having VAP and 17 (46 percent) as not having the condition. Quantitative culture of BAL effluent showed 90 percent sensitivity (18/20), 94.1 percent specificity (16/17), 94.7 percent positive predictive value and 88.8 percent negative predictive value. Fever and leukocytosis were useless for VAP diagnosis. Gram staining of BAL effluent was negative in 94.1 percent of the patients without VAP (16/17). Regarding the total cellularity of BAL, a cut-off point of 400,000 cells/ml showed a specificity of 94.1 percent (16/17), and a cut-off point of 50 percent of BAL neutrophils showed a sensitivity of 90 percent (19/20). In conclusion, BAL quantitative culture, Gram staining and cellularity might be useful in the diagnostic investigation of VAP

Diagnostic investigation of ventilator-associated pneumonia using bronchoalveolar lavage: comparative study with a postmortem lung biopsy.

The purpose of the present study was to validate the quantitative culture and cellularity of bronchoalveolar lavage (BAL) for the diagnosis of ventilator-associated pneumonia (VAP). A prospective validation test trial was carried out between 1992 and 1997 in a general adult intensive care unit of a teaching hospital. Thirty-seven patients on mechanical ventilation with suspected VAP who died at most three days after a BAL diagnostic procedure were submitted to a postmortem lung biopsy. BAL effluent was submitted to Gram staining, quantitative culture and cellularity count. Postmortem lung tissue quantitative culture and histopathological findings were considered to be the gold standard exams for VAP diagnosis. According to these criteria, 20 patients (54%) were diagnosed as having VAP and 17 (46%) as not having the condition. Quantitative culture of BAL effluent showed 90% sensitivity (18/20), 94.1% specificity (16/17), 94.7% positive predictive value and 88.8% negative predictive value. Fever and leukocytosis were useless for VAP diagnosis. Gram staining of BAL effluent was negative in 94.1% of the patients without VAP (16/17). Regarding the total cellularity of BAL, a cut-off point of 400,000 cells/ml showed a specificity of 94.1% (16/17), and a cut-off point of 50% of BAL neutrophils showed a sensitivity of 90% (19/20). In conclusion, BAL quantitative culture, Gram staining and cellularity might be useful in the diagnostic investigation of VAP.

Cerebrovascular reactivity and hypercapnic respiratory drive in diabetic autonomic neuropathy.

Because abnormalities in cerebrovascular reactivity (CVR) in subjects with long-term diabetes could partly be ascribed to autonomic neuropathy and related to central chemosensitivity, CVR and the respiratory drive output during progressive hypercapnia were studied in 15 diabetic patients without (DAN-) and 30 with autonomic neuropathy (DAN+), of whom 15 had postural hypotension (PH) (DAN+PH+) and 15 did not (DAN+PH-), and in 15 control (C) subjects. During CO(2) rebreathing, changes in occlusion pressure and minute ventilation were assessed, and seven subjects in each group had simultaneous measurements of the middle cerebral artery mean blood velocity (MCAV) by transcranial Doppler. The respiratory output to CO(2) was greater in DAN+PH+ than in DAN+PH- and DAN- (P < 0.01), whereas a reduced chemosensitivity was found in DAN+PH- (P < 0.05 vs. C). MCAV increased linearly with the end-tidal PCO(2) (PET(CO(2))) in DAN+PH- but less than in C and DAN- (P < 0.01). In contrast, DAN+PH+ showed an exponential increment in MCAV with PET(CO(2)) mainly >55 Torr. Thus CVR was lower in DAN+ than in C at PET(CO(2)) <55 Torr (P < 0.01), whereas it was greater in DAN+PH+ than in DAN+PH- (P < 0.01) and DAN- (P < 0.05) at PET(CO(2)) >55 Torr. CVR and occlusion pressure during hypercapnia were correlated only in DAN+ (r = 0.91, P < 0.001). We conclude that, in diabetic patients with autonomic neuropathy, CVR to CO(2) is reduced or increased according to the severity of dysautonomy and intensity of stimulus and appears to modulate the hypercapnic respiratory drive.

Impairment of the respiratory system in diabetic autonomic neuropathy.

Diabetic autonomic neuropathy (DAN) may affect up to 30% of the diabetic population. Sometimes DAN becomes clinically manifest causing specific symptoms and signs; more often, however, DAN is responsible for subtle alterations detectable only by functional tests, as in the case of the respiratory system. At first, abnormalities both in the bronchomotor tone and aspecific airway responsiveness to different stimuli were recognised in diabetic patients with DAN, indicating a defective control of mechanisms which regulate the bronchial calibre in these subjects. Subsequently, peculiar changes in breathing pattern and greater ventilatory requirements have been observed during incremental exercise in diabetics with DAN, suggesting an altered control of breathing in stressful conditions. Alterations in either peripheral or central chemosensitivity have been repeatedly shown in these patients, with marked differences related to the severity of DAN, concerning the neuro-muscular and ventilatory responsiveness to CO2. Following anecdotal reports, respiratory disturbances during sleep have been more carefully investigated in diabetic subjects and greater prevalence of sleep apnea, mainly in the obstructive form, has been found in the presence of DAN. The underlying mechanisms of sleep disordered breathing, however, are poorly understood in DAN and further studies are needed to elucidate them.

[Measuring cyclosporine levels in whole blood in kidney transplantation]. / Monitoramento dos níveis de ciclosporina em sangue total em transplantes renais.

BACKGROUND: Cyclosporin A is a potent immunosuppressive drug effective in combatting rejection following organ transplantation. In na effort to replace a radioimmunoassay (RIA) for whole blood determination of cyclosporine (Cya) we compared RIA with fluorescence polarization immunoassay (FPIAm). METHOD: 65 blood samples were analysed from kidney transplanted patients. The samples were collected into tubes containing EDTA as anticoagulant and analysed by RIA and FPIAm. RESULTS: The statistical analysis revealed a difference between both methods (p < 0.05). The linear-regression comparison of Cya concentration measured by RIA and FPIAm showed the following relationship: Cya(FPIAm) = 1.06 x Cya(RIA) + 5.8 (r = 0.9817). CONCLUSION: We conclude that FPIAm provides na alternative method for measuring cyclosporine in whole blood with the added advantages of being reasonably rapid, precise and easy to perform.

Renal haemodynamic responses to a chicken or beef meal in normal individuals.

BACKGROUND: In normal subjects, protein loading with soybean meal does not produce the same renal haemodynamic effects as those observed with a beef meal. The renal responses of an acute protein load in the form of chicken meal is unknown. METHODS: To examine whether the renal response to a chicken meal differs from that to beef, we studied the renal function of eight normal healthy volunteers before and after a protein load with each of these meals. In a crossover randomized study, we measured the glomerular filtration rate (GFR; inulin clearance), renal plasma flow (RPF; para-aminohippurate clearance) and, plasma amino acid and glucagon levels. We also determined the amino acid content of a sample of chicken and beef. RESULTS: GFR and RPF increased significantly 2 h after both the chicken and beef meals (chicken, 98+/-13 vs 119+/-18 and 476+/-123 vs 570+/-99 ml/min/1.73 m2; beef, 107+/-14 vs 122+/-16 and 501+/-118 vs 560+/-97 ml/min/1.73 m2, for GFR and RPF at basal and 2 h respectively, P<0.05). Renal vascular resistance decreased and the filtration fraction remained unchanged after both protein loads. The changes induced by the protein challenges in the plasma amino acid and glucagon levels were not different between the two protein sources. The amino acid contents of chicken and beef samples were similar. CONCLUSION: In normal subjects, chicken and beef meals induced a similar degree of hyperfiltration.

Monitoramento dos níveis de ciclosporina em sangue total en transplantes renais / Measuring cyclosporine in whole blood in kidney transplantation176-8

Introduçao e Objetivos. Ciclosporina A é uma droga imunossupressora potente e efetiva no combate à rejeiçao de órgaos transplantados. No presente estudo, os autores avaliaram o emprego de um imunoensaio monoclonal com fluorescência polarizada (FPIAm), como um método alternativo ao radioimunoensaio (RIA) para determinaçao dos níveis de ciclosporina em sangue total. Material e Métodos. Amostras de sangue de 65 pacientes submetidos a transplante renal foram colhidas em frascos com EDTA 12 horas após a última dose de ciclosporina, via oral. Os níveis de cilcosporina foram avaliados por meio de radioimunoensaio com anticorpo monoclonal e imunoensaio monoclonal com fluorescência polarizada. Resultados e Conclusao. A análise estatística revelou um coeficiente de correlaçao entre os métodos de r = 0,9817 e o teste t de Student pareado mostrou haver diferença estatisticamente significante entre eles (p<0,05). A análise da regressao revelou que os métodos poderiam ser comparáveis por meio da equaçao Cya(FPIAm) = 1,06xCya(RIA) + 5,8, mostrando que FPIAm é um excelente método alternativo ao RIA, com as vantagens de ser rápido, de fácil execuçao, reprodutível e com resultados comparavéis aos obtidos por RIA.

Influence of autonomic neuropathy of different severities on the hypercapnic drive to breathing in diabetic patients.

To investigate the effects of the autonomic nervous system on control of breathing, the neuromuscular (mouth occlusion pressure at 0.1 s after onset of inspiration [P0.1]) and ventilatory (minute ventilation [VE]) response to progressive hyperoxic hypercapnia was assessed in diabetic patients with autonomic dysfunction of different severity. Eighteen diabetics with autonomic neuropathy, nine with parasympathetic damage (DANp), and nine with parasympathetic and sympathetic damage (DANp+s), as indicated by marked postural hypotension, low increment of diastolic BP during sustained handgrip, and lowest resting catecholamine plasma levels, were studied together with a group of 10 diabetic patients without autonomic neuropathy (D) and a group of 10 normal subjects (C). All subjects had pulmonary function tests, including maximal voluntary ventilation and diffusion of carbon monoxide, measurements of respiratory muscle strength as maximal inspiratory mouth pressure (MIP) and maximal expiratory mouth pressure (MEP), and a CO2 rebreathing test (Read's method). Although in the normal range, lung volumes and FEV1 and forced expiratory flows were lower in the DANp and DANp+s groups than in the D and C groups, MIP and MEP were similar among C and diabetic groups, as well as resting P0.1, VE, tidal volume (VT), and respiratory rate (RR). The slope of the linear relationship between P0.1 and end-tidal PCO2 (PETCO2) was higher in DANp+s (0.63+/-0.07 cm H2O/mm Hg) than in C (0.45+/-0.06 cm H2O/mm Hg; p<0.05) and three times greater in DANp+s than in D (0.26+/-0.03 cm H2O/mm Hg; p<0.001) and DANp (0.24+/-0.03 cm H2O/mm Hg; p<0.001), who in turn showed a lower deltaP0.1/deltaPETCO2 than C. The VE increase with increasing PETCO2 was greater in DANp+s (3.70+/-0.85 L/min/mm Hg) than in DANp (2.13+/-0.20 L/min/mm Hg; p<0.05) and D (2.37+/-0.40 L/min/mm Hg; p=0.07), but not significantly higher from that of C (3.17+/-0.36 L/min/mm Hg). No differences were found for deltaVT/deltaPETCO2 among the groups, whereas the deltaRR/deltaPETCO2 relationship was steeper in DANp+s than in DANp (p<0.05) and D (p=0.055). These data reflect a depressed CO2 response both in D and DANp. The presumable decrease of the sympathetic nerve traffic in DANp+s appears to reverse this abnormality. DANp+s, however, exhibit an enhanced CO2 neuromuscular response even in respect to C, suggesting that the sympathetic nervous system might modulate the output of the respiratory centers to hypercapnic stimulus.

Long-term intensive therapy of IDDM patients with clinically overt autonomic neuropathy: effects on hypoglycemia awareness and counterregulation.

To test the hypothesis that hypoglycemia unawareness and impaired counterregulation are reversible after meticulous prevention of hypoglycemia in IDDM patients with diabetic autonomic neuropathy (DAN), 21 patients (8 without DAN [DAN-]; 13 with DAN [DAN+]; of the latter, 7 had orthostatic hypotension [DAN+PH+] and 6 did not [DAN+PH-]) and 15 nondiabetic subjects were studied during stepped hypoglycemia (plateau plasma glucose decrements from 5.0 to 2.2 mmol/l) before and 6 months after prevention of hypoglycemia (intensive therapy). After 6 months, frequency of mild hypoglycemia decreased from approximately 20 to approximately 2 episodes/patient-month while HbA1c increased from 6.2 +/- 0.3 to 6.9 +/- 0.2% (P < 0.05). Responses of adrenaline improved more in DAN- patients (from 1.17 +/- 0.12 to 2.4 +/- 0.22 nmol/l) than in DAN+PH- (from 0.75 +/- 0.25 to 1.56 +/- 0.23 nmol/l) and DAN+PH+ patients (from 0.80 +/- 0.24 to 1.15 +/- 0.27 nmol/l, P < 0.05) but remained lower than in nondiabetic subjects (4.9 +/- 0.37 nmol/l, P < 0.05), whereas glycemic thresholds normalized only in DAN-, not DAN+. Autonomic symptoms of hypoglycemia improved but remained lower in DAN- (6.2 +/- 0.6) than in nondiabetic subjects (8.1 +/- 1.1) and lower in DAN+PH+ (4 +/- 0.8) than in DAN+PH- subjects (5.1 +/- 0.8, P < 0.05), whereas neuroglycopenic symptoms normalized (NS). Cognitive function deteriorated less before than after prevention of hypoglycemia (P < 0.05). Thus, intensive therapy with emphasis on preventing hypoglycemia reverses hypoglycemia unawareness in DAN+ patients despite marginal improvement of adrenaline responses, results in low frequency of hypoglycemia despite impaired counterregulation, and maintains HbA1c in the range of intensive therapy. We conclude that DAN, long IDDM duration per se, and antecedent recent hypoglycemia contribute to different extents to impaired adrenaline responses and hypoglycemia unawareness.

Contribution of autonomic neuropathy to reduced plasma adrenaline responses to hypoglycemia in IDDM: evidence for a nonselective defect.

To determine the contribution of clinically overt diabetic autonomic neuropathy (DAN) to reduced plasma adrenaline responses to hypoglycemia in IDDM and to establish its selectivity for hypoglycemia, we studied 17 IDDM patients (7 without DAN [DAN-] and 10 with DAN [DAN+]), of whom 5 had and 5 did not have postural hypotension (DAN+PH+ and DAN+PH-, respectively), and 8 nondiabetic subjects on 2 different occasions, i.e., clamped hypoglycemia (steps from 5.0 to 2.2 mmol/l plasma glucose) and 30-min steady-state exercise at 55% V(O[2max]). Recent antecedent hypoglycemia was meticulously prevented before the studies to exclude hypoglycemia as a cause of reduced responses of adrenaline to hypoglycemia. In DAN- patients, maximal responses of adrenaline to hypoglycemia were reduced (2.44 +/- 0.58 nmol/l vs. 4.9 +/- 0.54 nmol/l in nondiabetic patients) (P < 0.05). In DAN+, adrenaline responses initiated at a lower plasma glucose and were lower than in DAN- (DAN+PH-, 1.06 +/- 0.38 nmol/l; DAN+PH+, 0.84 +/- 0.27 nmol/l; P < 0.001, but NS between PH- and PH+). In response to exercise, adrenaline increased less in DAN- (0.89 +/- 0.11 nmol/l) patients than in nondiabetic subjects (1.19 +/- 0.14 nmol/l; NS) and only to 0.36 +/- 0.07 nmol/l in DAN+PH- and 0.23 +/- 0.09 nmol/l in DAN+PH+ (P < 0.001 vs. DAN- and nondiabetic subjects). These results were confirmed when nondiabetic and DAN- subjects repeated the exercise at 60 watts (35 and 41% of V(O[2max]), respectively), i.e., at the same absolute workload of DAN+ patients. Thus, DAN (both PH+ and PH-) contributes to reduced responses of adrenaline to hypoglycemia independently of recent antecedent hypoglycemia. The adrenaline defect in DAN is not selective for hypoglycemia.

Cerebrospinal fluid profiles in acquired immunodeficiency syndrome with and without neurocryptococcosis.

Cryptococcosis is one of the most common fungal infections of the central nervous system (CNS) in AIDS patients and meningoencephalitis or meningitis is a frequently observed manifestation. However, systematic studies of cerebrospinal fluid (CSF) composition from AIDS patients with CNS cryptococcosis have been few. CSF samples from 114 HIV seropositive patients whose clinical complaint suggested CNS involvement, were analyzed; 32 samples from patients diagnosed as having neurocryptococcosis (Group 1) and 82 samples from patients with no identified neurological disfunction (Group 2). Based on cytological and biochemical results, two distinct profiles were observed: Normal (Group 1 = 31%, Group 2 = 39%); Abnormal (Group 1 = 69%, Group 2 = 61%). Lymphocytes were the most frequent cells in both groups. Our CSF cytological and biochemical findings showed that in AIDS patients liquoric abnormalities are quite frequent, non-specific and difficult to interpret. In these circumstances a systematic search to identify the etiologic agent using microbiological and/or immunological assays must be routinely performed.