Amoxicillin and clavulanic acid vs ceftazidime in the surgical extraction of impacted third molar: a comparative study.

The objective of this work is to compare the effectiveness and the side effects of two different drugs, amoxicillin and clavulanic acid vs ceftazidime, used as antibiotic prophylaxis in the surgical extraction of third molars and to demonstrate that the use of second choice antibiotic has no significant advantages in comparison with a first choice antibiotic. One hundred and seven patients with impacted third molar were selected and divided into two groups: amoxicillin and clavulanic acid were administered to group 1 and ceftazidime to group 2 for five days after surgery and we observed the postoperative period. The statistical analysis showed no differences between the two groups which lead to the conclusion that there is no indication to routinely administrate intramuscular second-choice antibiotic prophylatic therapy (ceftazidime) in case of surgical extraction of the third molar.

Association of Trp53 polymorphic variants at codon 72 with nonsyndromic mental retardation.

Mental retardation is the most common developmental disability affecting 2-3% of the population, a consequence of a wide range of genetic or nongenetic etiologic factors. The cause of mental retardation remains unknown in about 50% of cases. Trp53 (transformation related protein 53, also known as p53) is a tumor suppressor gene that activates the expression of genes involved in inducing growth arrest of cells in response to multiple forms of cellular stress and it plays a significant role in apoptotic cell death during the early development of the nervous system. In this study, we examined 246 children with nonsyndromic mental retardation from three Italian populations and 213 healthy children from the same populations. We observed that the Pro72/Pro72 genotype of p53 is much less represented in children with nonsyndromic mental retardation than in controls (6.5% versus 14.08%) (OR=0.42; 95% CI 0.21-0.83). These data suggest that subjects carrying the Pro allele are protected from this disease.

Contribution of postprandial versus interprandial blood glucose to HbA1c in type 1 diabetes on physiologic intensive therapy with lispro insulin at mealtime.

OBJECTIVE: To quantitate the contribution of postprandial blood glucose, which improves with the short-acting insulin analog lispro [Lys(B28),Pro(B29)] in type 1 diabetes, to the overall 24-h blood glucose concentration and the long-term HbA1c concentration under conditions of different postabsorptive blood glucose. RESEARCH DESIGN AND METHODS: A total of 24 type 1 diabetic patients on long-term intensive therapy with premeal human regular insulin (Hum-R) and bedtime NPH were randomly assigned to a continuation of Hum-R (group 1, n = 8), lispro (group 2, n = 8), or lispro + NPH (in variable proportions) administered at mealtime (group 3, n = 8) for 3 months, NPH administered at bedtime was continued in all three groups. Data from home blood glucose monitoring were collected, and a 24-h plasma glucose and insulin profile was obtained during a 2-day hospital visit to calculate areas under the postprandial glucose curve (3.5 h after breakfast, 3.5 h after lunch, and 3.0 h after dinner for a total of 10.0 h) and the postabsorptive blood glucose curve (the remaining 14.0 h out of 24.0 h) (AUC). Eight nondiabetic subjects were also studied. RESULTS: The substitution of Hum-R with lispro (group 2) resulted in lower postprandial blood glucose, but greater postabsorptive blood glucose (P < 0.05 vs. group 1). The postprandial blood glucose AUC was lower (161 +/- 19 vs. 167 +/- 20 mg.100 ml-1.h-1), but the postabsorptive blood glucose AUC was greater (155 +/- 22 vs. 142 +/- 19 mg.100 ml-1.h-1) (P < 0.05). Therefore, the 24-h blood glucose AUC was no different (NS). Consequently, HbA1c was no different (NS). This occurred because in group 2, mealtime lispro resulted in normal prandial plasma insulin, but also resulted in lower interprandial concentration (P < 0.05 vs. group 1). When NPH was added to lispro (30% at breakfast, 40% at lunch, 10% at dinner) in group 3, postabsorptive plasma insulin was similar to group 1 (NS), in group 3, the postprandial blood glucose AUC (153 +/- 17 mg.100 ml-1.h-1) was lower and the postabsorptive blood glucose AUC was no different, as compared with group 1 (NS). Therefore, the 24-h blood glucose AUC was lower (147 +/- 17 vs. 155 +/- 21 and 158 +/- 20 mg.100 ml-1.h-1), and HbA1c was lower (6.41 +/- 0.12 vs. 6.84 +/- 0.2 and 6.96 +/- 0.2% (groups 3, 1, and 2 respectively, P < 0.05). Frequency of hypoglycemia was greater in group 2 (P < 0.05), but not in group 3 (NS) vs. group 1.

Long-term intensive treatment of type 1 diabetes with the short-acting insulin analog lispro in variable combination with NPH insulin at mealtime.

OBJECTIVE: To establish whether the short-acting insulin analog lispro can be successfully implemented in long-term intensive insulin therapy in type 1 diabetes, and if so, what its effects are on glycemic control and frequency and awareness of hypoglycemia. RESEARCH DESIGN AND METHODS: We randomized 56 type 1 diabetic patients to treatment with either lispro (n = 28) or human regular insulin (Hum-R; n = 28) as mealtime insulin for 1 year (open design, parallel groups). Lispro was injected at mealtime and Hum-R was given 10-40 min before meals (bedtime NPH was continued on both occasions). With lispro, NPH was added at breakfast (approximately 70/30), lunch (approximately 60/40), and supper (approximately 80/20) (mixing percentage of lispro/NPH) to optimize premeal and bedtime blood glucose. RESULTS: Total daily insulin units were no different in the two treatment groups, but with lispro approximately 30% less short-acting insulin at meals and approximately 30% more NPH was needed versus Hum-R (P < 0.05). The bedtime NPH dosage was no different. With lispro + NPH, the mean daily blood glucose was lower than with Hum-R (8.0 +/- 0.1 vs. 8.8 +/- 0.1 mmol/l; P < 0.05), HbA1c was lower (6.34 +/- 0.10 vs. 6.71 +/- 0.11%, mean value over 1 year; P < 0.002), and hypoglycemia (blood glucose < or = 3.8 mmol/l) was less frequent (7.4 +/- 0.5 vs. 11.5 +/- 0.7 episodes/patient-month) and tended to occur more within 90 min after meals than in the postabsorptive state (P < 0.05 vs. Hum-R). After 1 year, plasma adrenaline and symptom responses to experimental, stepped hypoglycemia improved with lispro and were closer to the responses of 12 nondiabetic control subjects versus Hum-R both in terms of thresholds and magnitude (P < 0.05). CONCLUSIONS: We concluded that mealtime injection of lispro + NPH improves the 24-h blood glucose and the percentage HbA1c as compared with Hum-R. The improvement can be maintained long term. Intensive therapy with lispro + NPH results in less frequent hypoglycemia and better awareness and counterregulation of hypoglycemia.

Use of the short-acting insulin analogue lispro in intensive treatment of type 1 diabetes mellitus: importance of appropriate replacement of basal insulin and time-interval injection-meal.

To establish whether lispro may be a suitable short-acting insulin preparation for meals in intensive treatment of Type 1 diabetes mellitus (DM) in patients already in chronic good glycaemic control with conventional insulins, 69 patients on intensive therapy (4 daily s.c. insulin injections, soluble at each meal, NPH at bedtime, HbA1c <7.5%) were studied with an open, cross-over design for two periods of 3 months each (lispro or soluble). The % HbA1c and frequency of hypoglycaemia were assessed under four different conditions (Groups I-IV). Lispro was always injected at mealtime, soluble 10-40 min prior to meals (with the exception of Group IV). Bedtime NPH was continued with both treatments. When lispro replaced soluble with no increase in number of daily NPH injections (Group I, n = 15), HbA1c was no different (p = NS), but frequency of hypoglycaemia was greater (p < 0.05). When NPH was given 3-4 times daily, lispro (Group II, n = 18), but not soluble (Group III, n = 12) decreased HbA1c by 0.35 +/- 0.25% with no increase in hypoglycaemia. When soluble was injected at mealtimes, HbA1c increased by 0.18 +/- 0.15% and hypoglycaemia was more frequent than when soluble was injected 10-40 min prior to meals (Group IV, n = 24) (p < 0.05). It is concluded that in intensive management of Type 1 DM, lispro is superior to soluble in terms of reduction of % HbA1c and frequency of hypoglycaemia, especially for those patients who do not use a time interval between insulin injection and meal. However, these goals cannot be achieved without optimization of basal insulin.

Strategies toward improved control during insulin lispro therapy in IDDM. Importance of basal insulin.

OBJECTIVE: To examine whether overall glycemic control can be improved with insulin lispro by adjustment of the basal insulin regimen without an increased risk of hypoglycemia. RESEARCH DESIGN AND METHODS: A 5-month open study was performed in 66 IDDM patients after they had been transferred from human regular insulin to insulin lispro as a premeal therapy. The premeal and basal insulin regimens were adjusted according to self-monitoring of blood glucose during the visits at 2-week to 1-month intervals. Diurnal glucose profile, hypoglycemic events, HbA1c, and patient satisfaction were evaluated. RESULTS: The mean daily glucose level decreased from 9.2 +/- 0.2 to 8.4 +/- 0.2 mmol/l (P = 0.001) and HbA1c decreased from 8.8 +/- 0.1 to 8.0 +/- 0.1% (P < 0.001) (mean +/- SD). The number of daily NPH injections increased from 1.4 +/- 0.1 at baseline to 3.1 +/- 0.1 at the end of the study. Total daily insulin dose increased by 3 U (7%) because of an 8-U (43%) rise in basal insulin, whereas premeal insulin dose decreased by 5 U (20%). The number of hypoglycemic episodes did not change during the study. Of the patients, 86% considered insulin lispro equal or better than human regular insulin. CONCLUSIONS: Although the study was open, the date suggest that the appropriate combination of insulin lispro and basal insulin can improve postmeal hyperglycemia, HbA1c, and treatment satisfaction without increasing the risk of hypoglycemia.

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.

Evidence of increased systemic glucose production and gluconeogenesis in an early stage of NIDDM.

To assess the mechanisms of fasting hyperglycemia in NIDDM patients with mild elevation of fasting plasma glucose (FPG) compared with NIDDM patients with overt hyperglycemia, we studied 29 patients with NIDDM, who were divided in two groups according to their fasting plasma glucose (<7.8 and > or =7.8 mmol/l for groups A and B, respectively), and 16 control subjects who were matched with NIDDM patients for age, sex, and body mass index. All subjects were infused with [3-3H]glucose between 10:00 P.M. and 10:00 A.M. during overnight fasting to determine glucose fluxes. In 27 subjects (17 diabetic and 10 control), [U-14C]alanine was simultaneously infused between 4:00 A.M. and 10:00 A.M. to measure gluconeogenesis (GNG) from alanine. Arterialized-venous plasma samples were collected every 30 min for measurement of glucose fluxes, GNG, and glucoregulatory hormones. In group A, plasma glucose, rate of systemic glucose production (SGP), and GNG were greater than in control subjects (7.2 +/- 0.2 vs. 4.9 +/- 0.1 mmol/l, 10.9 +/- 0.2 vs. 9.5 +/- 0.3 micromol x kg(-1) x min(-1), and 0.58 +/- 0.04 vs. 0.37 +/- 0.02 micromol x kg(-1) x min(-1), respectively, for group A and control subjects; mean value 8:00 A.M.-10:00 A.M., all P < 0.05). Both increased SGP and GNG correlated with plasma glucose in all subjects (r = 0.77 and r = 0.75, respectively, P < 0.005). Plasma counterregulatory hormones did not differ in NIDDM patients compared to control subjects. The present studies demonstrate that SGP and GNG are increased in NIDDM patients without overt fasting hyperglycemia. Thus these metabolic abnormalities primarily contribute to early development of overnight and fasting hyperglycemia in NIDDM.

Effects of the short-acting insulin analog [Lys(B28),Pro(B29)] on postprandial blood glucose control in IDDM.

OBJECTIVE: To establish the effects of the short-acting insulin analog Lispro versus human regular insulin (Hum-R) on postprandial metabolic control in IDDM. RESEARCH DESIGN AND METHODS: Four studies were performed in 10 C-peptide-negative IDDM patients. Lispro or Hum-R (0.15 U/kg) or Lispro + NPH (0.07 U/kg) or Hum-R + NPH were injected subcutaneously 30 min (Hum-R) or 5 min (Lispro) before lunch. Preprandial plasma glucose (PG) was maintained on all four occasions at approximately 7.3 mmol/l by intravenous insulin. RESULTS: After subcutaneous Lispro injection, plasma free insulin (FIRI) was greater between 0 and 2 h (233 +/- 22 pmol/l) than after Hum-R (197 +/- 25 pmol/l) but lower between 2.25 and 7 h (81 +/- 10 vs. 104 +/- 13 pmol/l, P < 0.05). After Lispro, PG was lower versus Hum-R for 3 h (7.4 +/- 0.6 vs. 8.3 +/- 0.9 mmol/l) but subsequently increased more than after Hum-R (3.25-7h, 11.3 +/- 1 vs. 9.6 +/- 1.2 mmol/l), resulting in a 7-h postprandial PG greater than Hum-R (9.4 +/- 0.5 vs. 8.8 +/- 0.6 mmol/l) (all P < 0.05). Addition of NPH to Lispro increased the 2.5-to 7-h FIRI to 110 +/- 11 pmol/l and decreased the 3.25- to 7-h PG to 7.7 +/- 0.8 pmol/l, resulting in 0- to 7-h PG (7.3 +/- 0.3 mmol/l) lower than after Hum-R + NPH (7.9 +/- 0.5 pmol/l) (P < 0.05). CONCLUSIONS: At meals, in order for Lispro to improve postprandial blood glucose not only at 2-h, but also over a 7-h period in C-peptide-negative IDDM, basal insulin must be optimally replaced.

Long-term intensive insulin therapy in IDDM: effects on HbA1c, risk for severe and mild hypoglycaemia, status of counterregulation and awareness of hypoglycaemia.

UNLABELLED: The present studies were designed to assess the percentage of HbA1c, frequency, and awareness of hypoglycaemia (H) during long-term intensive therapy (IT) of insulin-dependent diabetes mellitus (IDDM). From 1981 to 1994, 112 IDDM patients were on IT. HbA1c was 7.17 +/- 0.16% (non-diabetic subjects 3.8-5.5%), the frequency of severe H 0.01 +/- 0.009 episodes/patient-year, frequency of mild symptomatic H 35.6 +/- 2.9 episodes/patient-year. IDDM patients with HbA1c < or = 5.5% (Group I, n = 10), between 6.1-7.0% (Group II, n = 12), and > or = 7.6% (Group III, n = 11) were studied to assess responses of counterregulatory hormones, symptoms and cognitive function during experimental, stepped H. Compared to 18 non-diabetic subjects, Group I exhibited high thresholds (plasma glucose had to decrease more than normal to evoke responses), and impaired responses of adrenaline, unawareness of H and delayed onset of cognitive dysfunction at the lowest glycaemic plateau (2.3 mmol/l). Group II had normal thresholds and responses, whereas Group III had low thresholds. Frequency of mild H was higher in Group I (54.5 +/- 1.9 episodes/patient-year) than in Group II and III (33.7 +/- 3.5 and 20.4 +/- 2.5 episodes/patient-year, respectively, p < 0.001) and correlated with percentage of HbA1c (r = -0.82). IN CONCLUSION: IT can maintain near-normal HbA1c and is compatible with low frequency of severe H. However, if HbA1c is less than 6.0%, mild, symptomatic H is excessively frequent and causes impaired counterregulation and H unawareness. Efforts should be made not only to maintain HbA1c < or = 7.0%, but also to prevent, recognize and reverse iatrogenic H unawareness during long-term IT of IDDM by maintaining HbA1c > 6.0%.

Relative roles of insulin and hypoglycaemia on induction of neuroendocrine responses to, symptoms of, and deterioration of cognitive function in hypoglycaemia in male and female humans.

To assess the relative roles of insulin and hypoglycaemia on induction of neuroendocrine responses, symptoms and deterioration of cognitive function (12 cognitive tests) during progressive decreases in plasma glucose, and to quantitate glycaemic thresholds, 22 normal, non-diabetic subjects (11 males, 11 females) were studied on four occasions: prolonged fast (n = 8, saline euglycaemia study, SA-EU), stepped hypoglycaemia (plasma glucose plateaus of 4.3, 3.7, 3 and 2.3 mmol/l) or euglycaemia during insulin infusion at 1 and 2 mU.kg-1.min-1 (n = 22, high-insulin hypoglycaemia and euglycaemia studies, HI-INS-HYPO and HI-INS-EU, respectively), and stepped hypoglycaemia during infusion of insulin at 0.35 mU.kg-1.min-1 (n = 9, low-insulin hypoglycaemia study, LO-INS-HYPO). Insulin per se (SA-EU vs HI-INS-EU), suppressed plasma glucagon (approximately 20%) and pancreatic polypeptide (approximately 30%), whereas it increased plasma noradrenaline (approximately 10%, p < 0.05). Hypoglycaemia per se (HI-INS-HYPO vs HI-INS-EU) induced responses of counterregulatory hormones (CR-HORM), symptoms and deteriorated cognitive function. With the exception of suppression of endogenous insulin secretion, which had the lowest glycaemic threshold of 4.44 +/- 0.06 mmol/l, pancreatic polypeptide, glucagon, growth hormone, adrenaline and cortisol had similar glycaemic thresholds (approximately 3.8-3.6 mmol/l); noradrenaline (3.1 +/- 0.0 mmol/l), autonomic (3.05 +/- 0.06 mmol/l) and neuroglycopenic (3.05 +/- 0.05 mmol/l) symptoms had higher thresholds. All 12 tests of cognitive function deteriorated at a glycaemic threshold of 2.45 +/- 0.06 mmol/l, but 7 out of 12 tests were already abnormal at a glycaemic threshold of 2.89 +/- 0.06 mmol/l. Although all CR-HORM had a similar glycaemic threshold, the lag time of response (the time required for a given parameter to increase) of glucagon (15 +/- 1 min) and growth hormone (14 +/- 3 min) was shorter than adrenaline (19 +/- 3 min) and cortisol (39 +/- 4 min) (p < 0.05). With the exception of glucagon (which was suppressed) and noradrenaline (which was stimulated), insulin per se (HI-INS-HYPO vs LO-INS-HYPO) did not affect the responses of CR-HORM, and did not influence the symptoms or the cognitive function during hypoglycaemia. Despite lower responses of glucagon, adrenaline and growth hormone (but not thresholds) in females than males, females were less insulin sensitive than males during stepped hypoglycaemia.

Mechanisms of arterial hypotension after therapeutic dose of subcutaneous insulin in diabetic autonomic neuropathy.

To assess whether a therapeutic, subcutaneous injection of insulin exerts hemodynamic effects in subjects with IDDM, 0.2 U/kg regular insulin was injected subcutaneously in 17 IDDM subjects: 6 without autonomic neuropathy, 7 with autonomic neuropathy and othostatic hypotension, and 4 with autonomic neuropathy but without orthostatic hypotension. Plasma glucose was maintained at approximately 8.5 mM throughout the studies. Mean blood pressure, plasma norepinephrine concentration, forearm vascular resistances, and calf venous volume were measured before and 120 min after subcutaneous insulin, in the supine position and 5 min after standing. Supine plasma volume ([125I]albumin and [131I]albumin) was measured before and after subcutaneous injection of insulin. In all three groups, subcutaneous insulin activated the sympathetic nervous system (approximately 30% increase in norepinephrine concentration). In subjects with IDDM but without autonomic neuropathy, standing forearm vascular resistance increased approximately 70% less after subcutaneous insulin, but supine or standing mean blood pressure did not decrease. In contrast, in subjects with IDDM with autonomic neuropathy and orthostatic hypotension, subcutaneous insulin decreased supine mean blood pressure (from 99 +/- 3 to 94 +/- 5 mmHg) and exaggerated the standing decrement in mean blood pressure (24 +/- 3 vs. 19 +/- 2 mmHg) (P < 0.05). This was associated with a decrease in forearm vascular resistance. Similarly, in subjects with IDDM with autonomic neuropathy without orthostatic hypotension, subcutaneously injected insulin decreased supine mean blood pressure (from 95 +/- 2 to 89 +/- 2 mmHg) and standing mean blood pressure by 8 +/- 1 mmHg (P < 0.05). Calf venous volume was not affected by subcutaneous insulin in any of the three groups. Plasma volume did not change after subcutaneous insulin in subjects with IDDM without autonomic neuropathy, whereas it decreased in those with autonomic neuropathy and orthostatic hypotension from 1.692 +/- 0.069 to 1.610 +/- 0.064 L/m2, without orthostatic hypotension from 1.631 +/- 0.027 to 1.593 +/- 0.024 L/m2, P < 0.05). No hemodynamic effects were observed when subjects with IDDM were restudied in a control experiment where placebo (distilled water), not insulin, was injected subcutaneously. In conclusion, therapeutic doses of subcutaneous insulin activate the sympathetic nervous system; decrease blood pressure in subjects with IDDM with autonomic neuropathy, but not in those without, primarily by decreasing arterial vascular resistances and plasma volume; and have no effects of capacitance vessels. Thus, in subjects with IDDM without autonomic neuropathy, greater activation of sympathetic nervous system after subcutaneous injection of insulin prevents orthostatic hypotension.(ABSTRACT TRUNCATED AT 400 WORDS)

Microbial response to crude oil and Corexit 9527: SEAFLUXES enclosure study.

The response of marine bacteria to Corexit 9527, with and without Prudhoe Bay crude oil labeled withn-(1-(14)C)hexadecane, in a temperate pelagic environment was monitored over 22 days using controlled ecosystem enclosures. The results indicated that Corexit and Corexit-dispersed crude oil stimulated bacterial production by serving as substrates and/or by inducing the release of organic compounds from the indigenous phytoplankton population. Highest bacterial standing stock was observed in the enclosure treated with a mixture of Corexit and crude oil, in which a large fraction of the predominant bacterivores were eliminated. Biodegradation appeared to be more significant than abiotic processes in contributing to the loss of low volatility n-alkanes in Corexit-dispersed oil. Twenty-two days following its addition, 50% of the radiotracer was recovered: 3% in the suspended particulate fraction, 10% in sedimentary material, 36% as CO2, and less than 1% in the dissolved organic pool.

Pregnancy and chronic obstructive pulmonary disease.

A 40-year-old pregnant patient with severe chronic obstructive pulmonary disease developed respiratory distress and delivered prematurely at 32 weeks' gestation. She required intubation and mechanical ventilation in the postpartum period. Aggressive management of this unusual case resulted in a successful outcome for both the patient and her child.