[Systemic toxicity caused by local anesthetics after peripheral nerve blocks]. / Toxicidad sistémica por anestésicos locales tras bloqueos de nervios periféricos.

Peripheral nerve blocks have aroused increasing interest in recent years, leading to a rise in the rate of complications. At the same time noteworthy technical advances have been made in areas such as nerve stimulation and ultrasound imaging, and local anesthetics have become safer. Nevertheless, the risk of anesthetic-related systemic toxicity, which manifests with neurological symptoms that tend to be forerunners of cardiovascular ones, can not be ignored. We report 2 cases of systemic toxicity due to the use of a mixture of local anesthetics during nerve blocks for outpatient surgery.

Toxicidad sistémica por anestésicos locales tras bloqueos de nervios periféricos / Systemic toxicity caused by local anesthetics after peripheral nerve blocks

Existe en los últimos años un interés creciente de los anestesiólogos por los bloqueos nerviosos periféricos, lo cual puede conllevar un incremento en la frecuencia de aparición de complicaciones. Al mismo tiempo hubo grandes avances tecnológicos (neuroestimulación, ultrasonografía…) y se incorporaron anestésicos locales cada vez más seguros, sin embargo, no podemos obviar el riesgo de toxicidad sistémica asociado, que habitualmente se manifiesta con síntomas neurológicos que suelen preceder a los cardiovasculares. Presentamos dos casos de toxicidad sistémica utilizando mezclas de anestésicos locales durante la realización de bloqueos nerviosos periféricos en cirugía ambulatoria

Peripheral nerve blocks have aroused increasing interest in recent years, leading to a rise in the rate of complications. At the same time noteworthy technical advances have been made in areas such as nerve stimulation and ultrasound imaging, and local anesthetics have become safer. Nevertheless, the risk of anesthetic-related systemic toxicity, which manifests with neurological symptoms that tend to be forerunners of cardiovascular ones, can not be ignored. We report 2 cases of systemic toxicity due to the use of a mixture of local anesthetics during nerve blocks for outpatient surgery

Bone mineral density in patients with type 1 diabetes mellitus.

Although osteopenia is often reported as a complication of type 1 diabetes mellitus, its frequency and severity remain unclear, and studies of bone mineral density in type 1 diabetics have yielded conflicting results. We measured bone mineral density at the lumbar spine and femoral neck in 88 Spanish adults with type 1 diabetes mellitus responsible for moderately severe complications. Mean age (+/- SD) was 28.9 +/- 8.8 years, and mean disease duration was 11.2 +/- 6.4 years. As compared to normal Spanish adults, bone mineral density was decreased in the patients at the lumbar spine (Z-score, -0.32 +/- 1.08; P < 0.001) but not at the femoral neck (Z-score, -0.21 +/- 1.03; P non-significant). The magnitude of bone loss in the diabetics was small (T-score, -0.38 +/- 1.13 at the lumbar spine and -0.37 +/- 1.08 at the femoral neck). Only three patients met WHO criteria for osteoporosis at one or both measurement sites. Patients with retinopathy (n = 37) had lower lumbar spine bone mineral density values than patients without retinopathy; however, this difference was no longer present after adjustment for age and disease duration. Bone mineral density values were similar in patients with (n = 13) and without microalbuminuria. Our findings suggest that bone loss is not a major problem in younger type 1 diabetics with short disease durations and no severe diabetic complications.

Acute pulmonary hemorrhage in infants associated with exposure to Stachybotrys atra and other fungi.

BACKGROUND: A geographic cluster of 10 cases of pulmonary hemorrhage and hemosiderosis in infants occurred in Cleveland, Ohio, between January 1993 and December 1994. STUDY DESIGN: This community-based case-control study tested the hypothesis that the 10 infants with pulmonary hemorrhage and hemosiderosis were more likely to live in homes where Stachybotrys atra was present than were 30 age- and ZIP code-matched control infants. We investigated the infants' home environments using bioaerosol sampling methods, with specific attention to S atra. Air and surface samples were collected from the room where the infant was reported to have spent the most time. RESULTS: Mean colony counts for all fungi averaged 29 227 colony-forming units (CFU)/m3 in homes of patients and 707 CFU/m3 in homes of controls. The mean concentration of S atra in the air was 43 CFU/m3 in homes of patients and 4 CFU/m3 in homes of controls. Viable S atra was detected in filter cassette samples of the air in the homes of 5 of 9 patients and 4 of 27 controls. The matched odds ratio for a change of 10 units in the mean concentration of S atra in the air was 9.83 (95% confidence interval, 1.08-3 X 10(6)). The mean concentration of S atra on surfaces was 20 X 10(6) CFU/g and 0.007 x 10(6) CFU/g in homes of patients and controls, respectively. CONCLUSION: Infants with pulmonary hemorrhage and hemosiderosis were more likely than controls to live in homes with toxigenic S atra and other fungi in the indoor air.

Kawasaki disease and the T-cell antigen receptor.

We investigated the evidence for an infectious etiology of Kawasaki disease (KD), an acute vasculitis of unknown etiology, by assessing the effects of KD on the T cell antigen receptor variable beta region families (V beta). Using 3-color flow cytometry, we studied KD patients pre- and post-intravenous gamma globulin (IVIG) therapy and at > 40 days post therapy, additionally comparing them to matched pediatric control patients (PCC) and their own healthy parents (one parent/KD child). Of all the V beta families examined, only V beta 2 exhibited statistically significant differences, between the pre- and post-IVIG samples and preIVIG and parent samples. No associations were found between V beta 2 findings and T cell memory, activation, or adhesion markers. For 2 KD patients, 4 parents, and 1 PCC participant, > 15% of resting CD8+ lymphocytes and > 15% of blastic CD8+ lymphocytes expressed a single V beta family, which varied by individual, without similar expansions in the CD4+ cell populations. One of the participants with this abnormality was the only one with significant cardiac abnormalities. For all participants with the V beta abnormality, other T-cell abnormalities were extensive and involved both CD4+ and CD8+ cells. We suggest that V beta 2 changes do occur in KD, as previously reported. However, these may not be involved in disease pathogenesis. Other V beta changes also occur. Those occurring in parents may reflect asymptomatic reinfection with an infectious agent causing KD. Further, some KD patients may have restricted cytotoxic T-cell responses to that as yet unidentified agent; this restricted response may be associated with more severe cardiac involvement.

Environmental risk factors associated with pediatric idiopathic pulmonary hemorrhage and hemosiderosis in a Cleveland community.

BACKGROUND: Unexplained pulmonary hemorrhage and hemosiderosis are rarely seen in infancy. A geographic cluster of 10 infants with this illness was identified in a large pediatric referral hospital in Cleveland, Ohio, during the period of January 1993 through December 1994. One infant died of severe respiratory failure. METHODS: A case-control study was conducted. Three control infants were matched by age with each case infant. All study infants' guardians were interviewed. Questions were asked about child care practices and home conditions for the period before case infants' illnesses. All infants' records were reviewed, their homes were visited, and a structural and environmental survey was conducted. RESULTS: All 10 case infants were black, and 9 were male, whereas 50.0% of control infants were male, and 83.3% were black. The case infants' mean age was 10.2 weeks (range, 6 weeks to 6 months). Matched analysis demonstrated that case infants' homes were more likely to have had water damage preceding the pulmonary hemorrhage event (odds ratio, 16.25; 95% confidence interval, 2.55 to infinity). Case infants were also more likely to have had close relatives with pulmonary hemorrhage (odds ratio, 33.14; 95% confidence interval, 5.10 to infinity). In addition, 50.0% of case infants experienced recurrent pulmonary hemorrhaging after returning to their homes. CONCLUSION: The results of this investigation of a cluster of infants with massive, acute pulmonary hemorrhage and hemosiderosis suggest that the affected infants may have been exposed to contaminants in their homes. Epidemiologic clues, such as water damage in the case infants' homes, suggest that environmental risk factors may contribute to pulmonary hemorrhage.

Diminished fraction of blockable ATP-sensitive K+ channels in islets transplanted into diabetic mice.

The reasons for the poor outcome of islet transplantation in diabetic patients are not well known; a better understanding of the pathophysiology of transplanted islets is needed. To study the mechanism coupling secretagogue stimuli with insulin release in transplanted islets, we determined the effects of glucose, tolbutamide, and carbamylcholine on the beta-cell membrane potential and cytosolic calcium concentrations ([Ca2+]i) of islets syngeneically transplanted into normal and streptozocin-induced diabetic mice. In both groups, normoglycemia was maintained after transplantation. Islets transplanted into normal recipients showed similar changes in beta-cell membrane potential and [Ca2+]i oscillations to those in control islets. In contrast, when islets were transplanted into diabetic mice, bursts of electrical activity were triggered at lower glucose concentrations (5.6 mmol/l) than in control islets (11 mmol/l), and maximal electrical activity was achieved at lower glucose concentrations (11 mmol/l) than in control islets (22 mmol/l). When membrane potential was plotted as a function of glucose concentration, the dose-response curve was shifted to the left. Compared with control islets, glucose-induced [Ca2+]i oscillations were broader in duration (22.3 +/- 0.6 s vs. 118.1 +/- 12.6 s; P < 0.01) and higher in amplitude (135 +/- 36 nmol/l vs. 352 +/- 36 nmol/l; P < 0.01). Glucose supersensitivity was attributed to a resting decrease in the fraction of blockable ATP-sensitive K+ (K+(ATP)) channels in transplanted islets that maintained normoglycemia with a limited beta-cell mass.

Trends and outcomes after prenatal diagnosis of congenital cardiac malformations by fetal echocardiography in a well defined birth population, Atlanta, Georgia, 1990-1994.

OBJECTIVES: In this study we used a population-based approach to assess the impact of fetal echocardiography on a well defined birth population with nearly complete ascertainment of cardiac defects. BACKGROUND: Although fetal echocardiography is being used more frequently in the prenatal diagnosis of congenital cardiac malformations, its impact on the diagnosis and surveillance of cardiac defects has not been described in defined populations. METHODS: All stillborn and live-born infants with diagnosed cardiac defects and whose mothers resided in the metropolitan Atlanta area from January 1990 through December 1994 were ascertained through an established birth defects surveillance system. All fetuses with cardiac defects diagnosed prenatally by a pediatric of cardiac defects, diagnostic trends and adverse fetal outcomes were described. RESULTS: We identified 1,589 infants with congenital cardiac malformations, for a live-birth prevalence rate of 8.1/1,000 (95% confidence interval [CI] 7.8 to 8.6). Overall, 97 (6.1%) of these cases of cardiac malformations were diagnosed prenatally. The proportion of cardiac defects diagnosed prenatally rose from 2.6% in 1990 to 12.7% in 1994, a nearly fivefold increase. The proportion of cardiac defects diagnosed prenatally during the study varied by the type of defect, from a low of 4.7% for atrial septal defects to a high of 28% for hypoplastic left heart syndrome. Prenatally diagnosed cardiac malformations were associated with a high incidence of infant mortality (30.9%, 95% CI 2.4 to 5.4) and fetal wastage (17.5%, 95% CI 6.2 to 11.3). CONCLUSIONS: These data show that fetal echocardiography is being used increasingly in the prenatal diagnosis of congenital cardiac malformations in metropolitan Atlanta. Few pregnancy terminations were reported as a result of such diagnoses. However, the study had limited power (10%) to detect a meaningful decrease in birth prevalence rates for congenital heart disease. In addition, survival of infants was not improved after prenatal diagnosis with fetal echocardiography.

Beta-cell growth and mass are preserved in long-term syngeneic islet transplantation in streptozocin-induced diabetic Lewis rats.

We determined beta-cell replication and mass in basal and stimulated conditions in long-term transplanted islets. Three groups of streptozocin-induced diabetic Lewis rats were transplanted with 1,000 islets (500 islets under left and right kidney capsules). At 2 (Tx-2), 5 (Tx-5), or 9 (Tx-9) months after transplantation, one of the two grafts (basal) was harvested; 14 days later, the contralateral graft (stimulated) was also harvested. Normoglycemia was achieved and maintained in all transplanted rats, although the capacity to respond to a glucose challenge deteriorated slightly 9 months after transplantation. Beta-cell replication remained stable in Tx-2, Tx-5, and Tx-9 basal grafts and was similar to replication in a control group of nontransplanted rats (0.28 +/- 0.06%); replication increased in Tx-2 (0.90 +/- 0.23%, P < 0.05) and Tx-9 (0.72 +/- 0.09%, P < 0.05) stimulated grafts. Beta-cell mass in basal grafts was similar to the initially transplanted mass (1.24 +/- 0.06 mg) and increased in stimulated grafts in Tx-2 (1.91 +/- 0.38 mg, P < 0.05) and Tx-5 (1.73 +/- 0.27 mg, P = 0.01) groups, compared with basal grafts, and in Tx-2 and Tx-9 groups (1.92 +/- 0.30 mg, P < 0.05), compared with initially transplanted mass. Therefore, beta-cell replication and mass were preserved up to 9 months after syngeneic transplantation, and beta-cells maintained the capacity to respond to increased metabolic demand, suggesting that replication is not a limiting factor in the survival of transplanted islets.

Ketoacidosis at diagnosis is predictive of lower residual beta-cell function and poor metabolic control in type 1 diabetes.

To determine the factors at diagnosis predictive of changes in residual beta-cell function and metabolic control in Type 1 diabetes, 125 patients older than 7 years of age consecutively diagnosed between March 1986 and June 1991 were followed prospectively for two years. The effect of age, gender and the presence of ketoacidosis (DKA) and islet-cell antibodies (ICA) on beta-cell function, metabolic control and insulin requirements were studied by multivariate analysis of variance (repeated measurements over time) in 90 patients who completed follow-up. DKA had an independent negative effect on residual beta-cell function over time (p = 0.001). ICA-positive patients had lower residual beta-cell function at the end of follow-up (p < 0.05), but overall differences were not significant. DKA and younger age had an independent negative influence on metabolic control (p < 0.05) and insulin requirements (p < 0.001) over time. It is concluded that residual beta-cell function in Type 1 diabetic patients two years after diagnosis was independently influenced by DKA and ICA at diagnosis. Moreover, DKA and age influenced metabolic control and could thus be used to predict those patients with rapidly deteriorating metabolic control who might benefit from a more intensive therapeutic approach.

Microalbuminuria is associated with limited joint mobility in type I diabetes mellitus.

OBJECTIVE: To determine whether limited joint mobility (LJM) is associated with microalbuminuria in type I diabetes mellitus. METHODS: Joint mobility was measured in a control group of 63 healthy subjects and in 63 type I diabetic patients, older than 18 years (mean 31.7 years, range 18-57), recruited from the outpatient clinic of the Endocrine Unit. Patients with established diabetic nephropathy (proteinuria or increased creatinine) were excluded. Joint mobility was assessed qualitatively with the prayer manoeuvre and quantitatively by measuring the angles of maximal flexion and extension of the fifth and third metacarpophalangeal (MCP) joints and wrist. Diabetic retinopathy was assessed by direct ophthalmoscopy. Urinary albumin excretion (UAE) was determined in at least two 24 hour urine samples. RESULTS: Joint mobility was limited in diabetic patients compared with control subjects. Diabetic patients with LJM had longer duration of diabetes (12.1 (SD 6.4) years compared with 6.9 (5.7) years; p < 0.001). Joint mobility was limited in patients with retinopathy: prayer manoeuvre was positive in 96.4% of patients with retinopathy, but in only 40.0% of patients with no retinopathy (p < 0.001); mobility of MCP joints and wrist was limited in diabetic patients with retinopathy even when the longer duration of their diabetes was taken into consideration. Microalbuminuria, present in 11 patients (17.5%), was associated with LJM: prayer manoeuvre was positive in 90.9% of patients with microalbuminuria, but in only 57.4% of patients with normal UAE (p < 0.05). Maximal flexion of MCP joints was reduced in patients with microalbuminuria. Microalbuminuria, but not LJM, was associated with risk factors of cardiovascular disease. CONCLUSION: LJM is associated with microalbuminuria and retinopathy in type I diabetes. The association is independent of age and duration of diabetes.

Transplanted beta cell response to increased metabolic demand. Changes in beta cell replication and mass.

We determined the capacity of transplanted beta cells to modify their replication and mass when stimulated by changes in metabolic demand. Five groups of Lewis rats were studied: group 1 (Tx-Px) had a 95% pancreatectomy 14 d after transplantation of 500 islets; group 2 (Px-Tx) had a 95% pancreatectomy 14 d before transplantation of 500 islets; group 3 (Tx) was transplanted with 500 islets; group 4 (Px) had a 95% pancreatectomy; and group 5 (normal) was neither transplanted nor pancreatectomized. Blood glucose was normal in Tx-Px and Tx groups at all times. Px-Tx and Px groups developed severe hyperglycemia after pancreatectomy that was corrected in Px-Tx group in 83% of rats 28 d after transplantation. Replication of transplanted beta cells increased in Tx-Px (1.15 +/- 0.12%) and Px-Tx (0.85 +/- 0.12%) groups, but not in Tx group (0.64 +/- 0.07%) compared with normal pancreatic beta cells (0.38 +/- 0.05%) (P < 0.001). Mean beta cell size increased in Tx-Px (311 +/- 14 microns2) and Px-Tx (328 +/- 13 microns2) groups compared with Tx (252 +/- 12 microns2) and normal (239 +/- 9 microns2) groups (P < 0.001). Transplanted beta cell mass increased in Tx-Px (1.87 +/- 0.51 mg) and Px-Tx (1.55 +/- 0.21 mg) groups compared with Tx group (0.78 +/- 0.17 mg) (P < 0.05). In summary, changes in transplanted beta cells prevented the development of hyperglycemia in Tx-Px rats. Transplanted beta cells responded to increased metabolic demand increasing their beta cell mass.

[Basal cortisol and ACTH in the immediate postoperative period in ACTH-producing hypophyseal adenomas]. / Interés del cortisol y ACTH basales en el postoperatorio inmediato de adenomas hipofisarios productores de ACTH.

BACKGROUND: Evaluate the usefulness of basal cortisol and ACTH during the immediate postoperative period following hypophyseal surgery, as early indicators of remission in patients with Cushing's disease. METHODS: Nine patients with Cushing's disease and on whom selective transphenoidal adenomectomy was performed were included in the study. Basal cortisol and ACTH levels were compared the first week after surgery, with definitive results being obtained after a month's time during which basal cortisol levels below 165 nmol/l indicated patients cured of Cushing's disease. RESULTS: Cortisol levels determined post-op, in five patients in remission, were found to be lower than those in patients who were not cured (63 +/- 55.8 versus 606 +/- 267 nmol/l, p < 0.01). However, ACTH levels were not lower. All the patients in remission had initial cortisol levels lower than 182 nmol/l, whereas the uncured patients had levels higher than 404 nmol/l. There was a correlation between cortisol measured in the first week and the definitive value (r = 0.81, p < 0.01). CONCLUSION: Cortisol in the immediate postoperative period following hypophyseal surgery is a good indicator of definitive adrenocorticotropic function and permits the identification of those patients in remission.

[Value of basal cortisol and ACTH in the immediate postoperative period of hypophyseal surgery in non-ACTH secretory adenomas]. / Interés del cortisol y de la ACTH basales en el postoperatorio inmediato de cirugía hipofisaria en adenomas no secretores de ACTH.

BACKGROUND: The aim of this study was to evaluate the usefulness of basal cortisol and ACTH in the immediate postoperative period of pituitary surgery as indicators of definitive adrenocorticotropin function. METHODS: Twenty-one patients with pituitary, non producers of ACTH, adenomas, three microadenomas and 18 macroadenomas treated by adenomectomy by a trans-sphenoidal route were respectively studied. The basal cortisol and ACTH were compared in the first week following surgery with the definitive results obtained after one month by dynamic tests (stimulation with ACTH or insulin hypoglycemia). RESULTS: The six patients with secondary adrenal failure (AF) in the definitive evaluation had lower basal cortisol in the immediate postoperative period than the patients with AF (135.3 +/- 225.3 nmol/l versus 473.6 +/- 147.2 nmol/l; p < 0.05). The values of ACTH were also lower (2.3 +/- 1.6 nmol/l versus 4.8 +/- 3.4; p < 0.05). In all the patients with definitive AF except one, the basal cortisol in the first week was lower than 130 nmol/l and in those who did not present AF it was greater than 220 nmol/l. CONCLUSIONS: In the immediate postoperative period after pituitary surgery cortisol is a good indicator of definitive adrenocorticotropin function. This parameter may identify the patients requiring posterior substitutive treatment.

Minimum number of islets required to maintain euglycemia and their reduced immunogenicity after transplantation into diabetic mice.

In streptozocin (SZ)-induced diabetic mice, 200 islets, but not 50 islets, consistently restore euglycemia within 1 week of transplantation. To determine the minimum number of islets sufficient to maintain euglycemia in a diabetic mouse, we first transplanted 50 and 150 syngeneic islets simultaneously into the right (RK) and left kidney (LK), respectively, and then removed the LK 1 week post-transplantation. The remaining 50 islets maintained euglycemia in 8 of 11 mice with normal intravenous glucose tolerance tests (IVGTT). Protection of 50 islets for at least 7 days was necessary because removal of the 150 islets at 5 or 3 days resulted in a much lower incidence of persistent euglycemia. Similarly, 25 islets were capable of maintaining euglycemia in 2 of 9 mice once hyperglycemia was reversed by split-transplantation of 25 (RK) and 175 (LK) islets. To examine if 50-islet allografts survive longer than 200-islet allografts, we split-transplanted 50 DBA/2 islets in the RK and 150 islets of either B6 (syngeneic), DBA/2 (allogeneic), or C3H/He (third party allogeneic) mouse origin in the LK in 3 groups of diabetic C57BL/6 (B6) mice. The survival of 50 DBA/2 islets in each group after removal of the LK on day 7 was compared to that of 200 DBA/2 islets in control B6 mice. Maximum prolongation of allograft survival was obtained with 50 DBA/2 islets that were split-transplanted with syngeneic B6 islets. These results clearly demonstrate that 50 islets are sufficient to maintain normal glucose tolerance once euglycemia is induced by transplantation of a larger number (i.e., 200) of islets and that 50 islet allografts are much less immunogenic than 200-islet allografts.