Synthesis and characterization of cyclohexane-1R,2R-diamine-based Pt(iv) dicarboxylato anticancer prodrugs: their selective activity against human colon cancer cell lines.

Three pairs of asymmetric dicarboxylato derivatives based on the cisplatin and oxaliplatin-like skeletons have been synthesized de novo or re-synthesized. The axial ligands consist of one medium-chain fatty acid (MCFA), namely clofibrate (i.e. 2-(p-chlorophenoxy)-2-methylpropionic acid, CA), heptanoate (HA) or octanoate (OA), respectively, and an inactive acetato ligand that imparts acceptable water solubility to such conjugates. Stability tests provided evidence for the partial formation of two hydrolyzed products, corresponding to two monoaqua diastereomers derived from the substitution of an equatorial chlorido ligand with a water molecule. The complexes have been tested on three different colon cancer cell lines having different histological history, and also on the cisplatin-sensitive A2780 ovarian cancer cell line for comparison. This allowed the evaluation not only of the increase in activity on passing from Pt(ii) to Pt(iv) derivatives, but also the selectivity towards colon cancer cells brought about by the cyclohexane-1R,2R-diamine carrier ligand.

How to obtain Pt(iv) complexes suitable for conjugation to nanovectors from the oxidation of [PtCl(terpyridine)].

Oxidation of [Pt(II)Cl(terpy)]+ (terpy = 2,2':6',2''-terpyridine) has been attempted with several oxidizing agents and under different experimental conditions in order to obtain a Pt(iv) complex suitable for the conjugation to nanovectors to be used in drug delivery targeting for anticancer therapy. The best compromise in terms of yield and purity of the final complex was obtained by microwave-assisted reaction at 70 °C in 50% aqueous H2O2 for 2 h. Under these conditions the quantitative formation of [Pt(IV)Cl(OH)2(terpy)]+ was observed. The subsequent synthetic steps were, (i) functionalization of [Pt(IV)Cl(OH)2(terpy)]+ in the axial position with succinic anhydride to obtain [Pt(IV)Cl(OH)(succinato)(terpy)]+ and (ii) reaction of the latter with nonporous silica nanoparticles (SNPs) with an external shell containing primary amino groups to obtain a nanovector able to transport the Pt(iv) antitumor prodrug in the form of a conjugate Pt-SNP. Finally, the antiproliferative activity and cell accumulation of [Pt(II)Cl(terpy)]+, [Pt(IV)Cl(OH)2(terpy)]+, and the Pt-SNP conjugate were measured on three cancer cell lines. Despite highly effective accumulation of Pt-SNP in cells, a modest increase in activity was observed with respect to the molecular species. Further experiments showed that the Pt-SNP conjugate can release [Pt(II)Cl(terpy)]+ upon reduction, but this metabolite may undergo hydrolysis, and the resulting aquo complex could coordinate once again the free amino groups of the SNPs. In the resulting tetraamine form, the Pt(ii) complex conjugated to the SNPs cannot completely perform its antiproliferative activity.

Cisplatin and valproate released from the bifunctional [Pt(IV)Cl2(NH3)2(valproato)2] antitumor prodrug or from liposome formulations: who does what?

The cisplatin-sensitive human ovarian cancer cells A2780 have been challenged with cationic liposomes containing the single drug cisplatin or valproate or their combination with an approximate 1 : 2 molar ratio, i.e. the same ratio present in preformed (OC-6-33)-diamminedichloridobis(valproato)platinum(iv), that releases such metabolites by intracellular Pt(iv) → Pt(ii) reduction. The results of this comparison confirm that valproate barely penetrates cells unless it is transported by liposomes or it is coordinated to a lipophilic Pt(iv) assembly. The two drugs have a synergistic action, cisplatin being the more potent antiproliferative agent. Even if the preformed (OC-6-33)-diamminedichloridobis(valproato)platinum(iv) releases cisplatin and valproate in the same amount as the liposome formulation, the Pt(iv) derivative is more active. This important feature, common to all Pt(iv) complexes having very lipophilic carboxylates, is attributable to their propensity to remain in cells and to continuously bind DNA, unlike cisplatin that is partially removed from cells by efficient efflux pathways.

Functionalized nonporous silica nanoparticles as carriers for Pt(iv) anticancer prodrugs.

Nonporous silica nanoparticles (SNPs) with an external shell containing primary amino groups were proposed as potential delivery systems for Pt(iv) antitumor prodrugs. Spherical SNPs containing two different external arms, i.e. 3-aminopropyl and N-(6-aminohexyl)aminomethylene, of around 125 nm hydrodynamic diameter were loaded with two different cisplatin-based Pt(iv) complexes, namely (OC-6-44)-diamminedichloridoethoxidosuccinatoplatinum(iv) and (OC-6-44)-diamminedichloridoacetylamidosuccinatoplatinum(iv), through the formation of amide bonds between the pendant amino groups on SNPs and the free carboxylic group of the complexes. In the presence of the N-(6-aminohexyl)aminomethylene arm, the Pt(iv)-SNP conjugates showed a negligible (unwanted) Pt release by hydrolysis, whereas in the presence of ascorbic acid the reduction of Pt(iv) → Pt(ii) caused the substantial release of the active metabolite cisplatin. Conjugate Pt(iv)-SNP exhibited better antiproliferative activity on the Pt-sensitive A2780 human ovarian cancer cell line than the parent cisplatin and their free Pt(iv) precursors, due to their more efficient cellular uptake, likely by endocytosis.

[Risk and prevention of diabetic nephropathy]. / Rischio e prevenzione della nefropatia diabetica.

Diabetic nephropathy is one of the most frequent causes of end-stage renal disease (ESRD), and there has been a dramatic increase in the number of patients entering renal replacement therapy in the last few years. Moreover, diabetic nephropathy is associated with elevated cardiovascular morbidity and mortality. Prevention and treatment of diabetic nephropathy is based on optimal metabolic and blood pressure control, proteinuria reduction, and renin-angiotensin-aldosterone system (RAAS) inhibition. In the normoalbuminuric patient, optimal glycemic control (HbA1c below 7.0%) plays a fundamental role in the primary prevention of ESRD. Furthermore, blood pressure levels below 130/80 mmHg are strongly recommended. In the microalbuminuric stage, strict glycemic control (HbA1c below 7.0%) likely reduces the incidence of overt nephropathy, while blood pressure values less than 130/80 mmHg are recommended. Moreover, there is evidence that inhibition of RAAS, either by angiotensin-converting-enzyme inhibitors (ACE-I) or angiotensin-receptor blockers (ARB), reduces the development of overt nephropathy, regardless of the blood pressure levels. ACE-I are recommended as the drugs of choice in type 1 diabetes, while both ACE-I and ARB are considered first-choice drugs in type 2 diabetes. Once overt proteinuria has developed, it is uncertain whether glycemic control affects the progression of nephropathy, which is strongly influenced by blood pressure and proteinuria. Optimal blood pressure levels are < 130/80 mmHg in patients with proteinuria < 1 g/day and < 120/75 mmHg in patients with proteinuria > or =1 g/day. In type 1 diabetes there is consensus on the renoprotective role of ACE-I, while in type 2 diabetes, ARB have been shown to be more effective than conventional therapy or calcium-channel blockers in slowing the progression of nephropathy. Lastly, a multifactorial therapeutic approach based on optimal glycemic control, intensive antihypertensive therapy, inhibition of RAAS, statins and aspirin is pivotal in the prevention and treatment of diabetic nephropathy.

[Primary eosinophilic enteritis: a case report]. / Enteritis eosinofílica primaria: a propósito de un caso.

Primary eosinophilic enteritis is a rare entity that is characterized by eosinophil infiltration in the different layers of the small bowel. The symptoms depend on the site of infiltration and the layers affected. High blood levels of eosinophils are usually present. Computed tomography plays a fundamental role in the evaluation of this disease. We present a case of primary eosinophilic enteritis diagnosed on the basis of clinical, laboratory, and CT findings.

Creatinine clearance and signs of end-organ damage in primary hypertension.

A reduction in renal function is associated with high cardiovascular morbidity and mortality in hypertension. The aim of the present study was to investigate the relationship between creatinine clearance and subclinical organ damage in 957 never previously treated, middle-aged patients with primary hypertension. Renal function was estimated by means of the serum creatinine level using the Cockcroft-Gault formula; left ventricular hypertrophy (LVH) was determined according to electrocardiographic criteria; and retinal vascular changes were evaluated by direct ophthalmoscopy. Creatinine clearance was, on the average, 83+/-21.2 ml/min, and the prevalence of LVH and retinopathy was 13 and 49%, respectively. Creatinine clearance was inversely related to the duration of disease (r=-0.132, P<0.0001), systolic blood pressure (r=-0.110, P=0.001), serum glucose (r=-0.090, P=0.007), total cholesterol (r=-0.196, P<0.0001), and LDL-cholesterol (r=-0.196, P<0.0001). Patients in the lower quintile of creatinine clearance showed a higher prevalence of electrocardiogram (ECG) determined LVH (P=0.04), as well as retinal changes (P=0.02). The risk of having LVH or retinal vascular changes increases significantly with each s.d. decrease in creatinine clearance, regardless of traditional cardiovascular risk factors. Moreover, patients with ECG-determined LVH and retinal changes showed lower creatinine clearance as compared to those with lesser degrees of target organ involvement (P<0.01). In conclusion, a mild reduction in creatinine clearance is associated with preclinical end-organ damage in patients with normal creatinine and primary hypertension. These data may help explain the high cardiovascular mortality observed in patients with renal dysfunction. Routine evaluation of creatinine clearance could be useful for identifying patients at higher cardiovascular risk.

Long-lasting antithrombotic effects of a single dose of human recombinant, active site-blocked factor VII: insights into possible mechanism(s) of action.

Tissue factor (TF) is important in initiating intravascular thrombosis. We demonstrated that active-site blocked factor VII (FVIIai) inhibits intravascular thrombosis for at least 6 h following a single injection, despite FVIIai plasma half-life was approximately 45 min. The aims of the present study were: (a) to determine the duration of the antithrombotic effects of a single injection of FVIIai; and (b) to assess whether FVIIai prolonged effects can be explained by a slow dissociation rate from TF in the arterial wall. Cyclic flow variations (CFVs), obtained in stenotic rabbit carotid arteries with endothelial injury, were abolished by either FVIIai (100 micro g kg-1 min-1 for 10 min) or hirudin (1 mg kg-1). After CFVs were abolished, carotid blood flow velocity was recorded continuously for 24 h. CFVs restored in all hirudin-treated animals after 2.1 +/- 0.3 h, while they restored in only four of nine FVIIai-treated rabbits in 10.1 +/- 2.2 h. Five animals in this group did not show restoration of CFVs up to 24 h. Immunohistochemistry revealed that FVIIai was still bound to the arterial wall 24 h following its administration, despite at this time FVIIai plasma levels were undetectable. Prothrombin time and partial thromboplastin time did not change significantly. FVIIai exerts potent, long-lasting antithrombotic effects without affecting systemic hemostatic parameters; a possible mechanism is a slow dissociation rate of FVIIai from TF. These proprieties make FVIIai particularly attractive as an antithrombotic intervention.

Microalbuminuria is an integrated marker of subclinical organ damage in primary hypertension.

Increased urine albumin excretion is associated with an unfavourable cardiovascular risk profile and prognosis in primary hypertension, even though its pathogenesis is currently unknown. Microalbuminuria (Mi) has been proposed as an integrated marker to identify patients with subclinical organ damage, but its routine use is still too often neglected in clinical practice. The aim of our study was to evaluate the relationship between urinary albumin excretion and early signs of subclinical target organ damage (TOD), namely left ventricular hypertrophy and carotid atherosclerosis in a large group of non diabetic hypertensive patients. A group of 346 never treated patients with primary hypertension (212 men, 134 women, mean age 47 +/- 9 years) referred to our clinic were included in the study. They underwent the following procedures: (1) family and personal medical history and physical examination; (2) clinical blood pressure measurement; (3) routine blood chemistry and urine analysis including determination of urinary albumin excretion (ACR); (4) electrocardiogram; (5) ultrasound evaluation of left ventricular mass (LVMI) and carotid artery thickness (IMT). The overall prevalence of Mi, left ventricular hypertrophy, and carotid plaque was 13, 51, and 24% respectively. Mi was significantly correlated with LVMI (P < 0.0001), IMT (P < 0.0001) and several metabolic and non-metabolic risk factors (blood pressure, body mass index, serum lipids). Cluster analysis identified three subgroups of patients who differ significantly with regards to TOD and albuminuria (P < or = 0.001 for each of the examined variables). Patients with higher IMT and LVMI values also showed increased ACR levels. Furthermore, patients with microalbuminuria were more likely to have both LVH and IMT values above the median for the study population (OR 21, C.I. 4.6-99.97, P < 0.0001). Mi is an integrated marker of subclinical organ damage in patients with primary hypertension. Evaluation of urinary albumin excretion is a specific, cost-effective way to identify patients at higher risk for whom additional preventive and therapeutic measures are advisable.

Impact of insecurity, the AIDS epidemic, and poverty on population health: disease patterns and trends in Northern Uganda.

A retrospective analysis of the discharge records of 186,131 inpatients admitted to six Ugandan hospitals during 1992-1998 was performed to describe the disease patterns and trends among the population of Northern Uganda. In all hospitals, malaria was the leading cause of admission and the frequency of admissions for malaria showed the greatest increase. Other conditions, such as malnutrition and injuries, mainly increased in the sites affected by civil conflict and massive population displacement. Tuberculosis accounted for the highest burden on hospital services (approximately one-fourth of the total bed-days), though it showed a stable trend over time. A stable trend was also observed for acquired immunodeficiency syndrome (AIDS), which is in contrast to the hypothesis that AIDS patients have displaced other patients in recent years. In conclusion, preventable and/or treatable communicable diseases, mainly those related to poverty and poor hygiene, represent the leading causes of admission and death, reflecting the socioeconomic disruption in Northern Uganda.

5,10-Methylenetetrahydrofolate reductase polymorphism and early organ damage in primary hypertension.

Hyperhomocyst(e)inemia is a known risk factor for the development of atherosclerotic vascular damage. Plasma homocyst(e)ine levels are influenced by nutritional and hereditary factors. A point mutation (cytosine to thymidine substitution; C677T) in the gene encoding 5,10-methylenetetrahydrofolate reductase (MTHFR) makes the enzyme thermolabile and has been associated with elevated homocyst(e)ine levels in homozygous carriers (TT genotypes). We evaluated the relationship between the T allele encoding for the thermolabile variant of MTHFR and several biochemical risk factors and early signs of hypertensive and atherosclerotic organ damage in 206 untreated patients with primary hypertension. The MTHFR genotype was evaluated by polymerase chain reaction. Albuminuria was measured as albumin-to-creatinine ratio in three nonconsecutive first morning urine samples (negative urine culture). Persistent Mi (Alb+) was defined as an average albumin-to-creatinine ratio between 2.38 and 19 (men) and 2.96 and 20 (women). Left ventricular (LV) mass index (LVMI) was assessed by M-B mode echocardiography (LV hypertrophy, LVH = LVMI > or = 125 g/m2), carotid geometry by high-resolution ultrasound scan, and retinal vascular changes by direct ophthalmoscopy (Keith-Wagener classification). The prevalence of Mi, LVH, and retinopathy was 14%, 45%, and 42%, respectively. The prevalence of carotid plaque was 25%. Allele frequencies for C (wild-type allele) and T allele (mutant allele) were 56% and 44%, respectively. Genotype frequencies were CC 29%, CT 54%, TT 17% according to Hardy Weinberg equilibrium. There were no differences as for age, sex, body mass index, blood pressure levels, lipid profile, smoking habits, and alcohol intake, and LVMI and urinary albumin excretion on the basis of MTHFR genotype. Patients with TT polymorphism showed a higher prevalence of retinal vascular changes (TT, 61% v CT + CC, 38%; P < .02) and carotid plaque (TT, 42% v CT + CC, 21%; P < .05) compared to patients with CC and CT polymorphism. Moreover, patients with T allele showed increased carotid artery size as demonstrated by intima plus media thickness (IT, 0.79 +/- 0.05 mm v CT + CC, 0.67 +/- 0.02 mm; P < .02), relative wall thickness (TT, 0.23 +/- 0.01 mm v CT + CC, 0.20 +/- 0.005 mm; P < .02), and surface area (TT, 19 +/- 1.9 mm2 v CT + CC, 15 +/- 0.55 mm2; P < .05). Multiple linear regression analysis demonstrated that MTHFR genotype and systolic blood pressure independently influence intima-media thickness and together account for about 11% of its variations (r2 = 0.11, F = 9.7, dF = 1-205, P < .0001). Homozygosity for the T allele of the MTHFR gene is an independent risk factor for the development of early atherosclerotic organ damage in hypertensive patients.

Long term effect of nifedipine GITS and lisinopril on subclinical organ damage in patients with essential hypertension.

BACKGROUND: Preventing subclinical organ damage is currently a major issue in the management of patients with essential hypertension. Antihypertensive drugs which act through different pathophysiological mechanisms might confer specific target organ protection beyond what is already provided by their blood pressure lowering effect. METHODS: Thirty-one patients with essential hypertension were randomized to receive long-term treatment with either a calcium channel blocker (nifedipine GITS, 90 mg/day) or an ACE-inhibitor (lisinopril, 20 mg/day). Blood pressure, left ventricular mass, carotid wall thickness and timed urinary albumin excretion were measured at baseline and over the course of 24 months of treatment. RESULTS: Both regimens significantly lowered mean blood pressure over the 24 months (from 124+/-2 to 103+/-2 mmHg in the lisinopril group and from 122+/-2 to 104+/-1 in the nifedipine group). Overall, end-organ damage improved with persistent blood pressure control. However, the two treatments had different specific effects. Lisinopril induced a more pronounced reduction of the left ventricular mass index (from 56+/-3 to 52+/-2 g/m2.7, P< 0.05) and urinary albumin excretion (from 34+/-15 to 9+/-2 microg/min, P< 0.01), while nifedipine achieved a greater reduction of carotid intima plus media thickness (from 0.8+/-0.06 to 0.6+/-0.06 mm, P< 0.01). CONCLUSIONS: Blood pressure control does help reduce the severity of organ damage in patients with essential hypertension. Different antihypertensive treatments may confer additional specific cardiorenal and vascular protection regardless of blood pressure control. These data could be useful when devising individualized therapeutic strategies in high-risk hypertensive patients.

Comparative study between children with and without cleft lip and cleft palate, part 1: cephalometric analysis.

OBJECTIVE: This study was conducted to compare craniofacial relationships, position, and curvature of the cervical spine between children with cleft lip and cleft palate who had been operated on and children without clefts. METHOD: This study was performed in 28 children with mixed dentition. They were divided into two groups. The study group included 14 children with unilateral operated cleft lip and cleft palate, ranging in age from 6 to 12 years, who clinically presented with a short upper lip, abnormal lip seal, and inhibition of sagittal development of the midface that was radiographically assessed. The control group included 14 children without clefts, ranging in age from 8 to 11 years. All of them had normal lip seal, nasal breathing, and a clinically normal body posture. DESIGN: A lateral craniocervical radiograph in a self-balanced natural head position in an erect posture, and without using a head holder, was taken for each child of both groups, with the mandible in maximum intercuspation and lips in habitual posture. The true vertical was marked on all the films. Specific angular and linear dimensions were used to assess the craniocervical relationships, as were the position of the cervical spine, its curvature, or both. RESULTS AND CONCLUSIONS: The study group presented a significant increase in the extension of the head on the neck, forward position of the cervical spine, and a decrease in the curvature of the cervical spine in comparison with the children without clefts. These results are more relevant considering that the study group also presented higher significant values of lower facial height than children without clefts.

Comparative study between children with and without cleft lip and cleft palate, part 2: electromyographic analysis.

OBJECTIVE: This study was conducted to compare electromyographic (EMG) activity of superior orbicularis oris muscle between children with repaired cleft lip and cleft palate and children without clefts. METHODS: This study included 28 children with mixed dentition. They were divided into two groups. The study group included 14 children with repaired unilateral cleft lip and cleft palate, ranging in age from 6 to 12 years, who presented clinically with a short upper lip, abnormal lip seal, and inhibition of sagittal development of the midface as assessed radiographically. The control group included 14 children without clefts ranging in age from 8 to 11 years. All had normal lip seal, nasal breathing, and a clinically normal body posture. DESIGN: Bipolar surface electrodes were used for EMG recordings of resting level activity and during swallowing of saliva, speech, and chewing and swallowing of an apple. RESULTS AND CONCLUSIONS: A significantly higher level of activity at rest and during swallowing of saliva was observed in the cleft lip and cleft palate group. Similar activity during speech and chewing and swallowing of an apple was observed in both groups. The higher level of activity at rest and during swallowing of saliva in children with cleft lip and cleft palate seems to suggest that upon higher functional demands their activity increases less than in children without clefts. From a clinical point of view, if increased EMG activity at rest and during swallowing of saliva reflects increased force on the maxilla, then our findings may corroborate Bardach's findings (1990) that surgical treatment of cleft lip has an iatrogenic effect on facial growth, although the lack of significant correlation between the cephalometric data and EMG findings in the present study.

Effects of recombinant active site-blocked activated factor VII in rabbit models of carotid stenosis and myocardial infarction.

We tested the effects of human recombinant active site-blocked activated factor VII (rFVIIai) in a rabbit model of carotid artery thrombosis. Cyclic flow variations (CFVs), due to recurrent thrombus formation, were obtained in stenotic rabbit carotid arteries with endothelial injury. After 30 min of CFV, the animals received rFVIIai. If CFVs were abolished, animals were observed for 30 additional minutes, after which human recombinant activated factor VII was infused into the carotid artery to determine whether it could displace rFVIIai from tissue factor (TF), thus restoring CFV. An additional group of animals received rFVIIai to determine its duration of action. Recombinant FVIIai abolished CFVs in 8 of 9 rabbits (P < 0.01). This effect was reversible, as rFVIIa administration restored CFVs in all animals. A further study was initiated to assess whether TF-dependent reductions in coronary blood flow might contribute to the occurrence of myocardial injury during postischaemic reperfusion of rabbit hearts. Recombinant FVIIai resulted in significant reductions in both infarct size and no-reflow area, while rFVIIa produced a significant increase in both infarct size and no-reflow area. These data suggest that rFVIIai might be beneficial in patients with acute myocardial infarction undergoing reperfusion therapies.

Genetic polymorphism of the renin-angiotensin system and organ damage in essential hypertension.

BACKGROUND: The renin-angiotensin-aldosterone system (RAAS) plays a significant role in the development of hypertensive cardiac and vascular remodeling. Recently, several genetic variants of its key components, which may be clinically relevant and thus prove to be useful in the evaluation of cardiovascular risk, have been described. We therefore investigated the association between ACE I/D, AGT M235T, and AT1 A1266C gene polymorphisms and early signs of target organ damage in 215 untreated patients with essential hypertension (EH). METHODS: Genotyping was based on the polymerase chain reaction technique, with further restriction analysis when required. Albuminuria was measured as the albumin-to-creatinine ratio (ACR). The left ventricular mass index (LVMI) was assessed by echocardiography (LVH = LVMI > or = 125 g/m2), carotid wall thickness (IMT) by an ultrasonographic (US) scan, and retinal vascular changes by direct ophthalmoscopy (Keith-Wagener classification). RESULTS: The prevalence of microalbuminuria (Mi), LVH, and retinal vascular changes was 14, 46, and 74%, respectively. ACE, AGT, and AT1 genotype distribution was in agreement with the Hardy-Weinberg equilibrium. There was no difference in age, duration of disease, body mass index (BMI), blood pressure, and lipid profile when data were analyzed on the basis of genotype. Serum levels of angiotensin-converting enzyme (ACE) were related to the ACE genotype (10.2 +/- 0.5, DD; 8.2 +/- 0.3, ID; 6.5 +/- 0.4 IU/mL, II; P < 0. 0001 by analysis of variance). The ACE genotype independently influences serum ACE levels and accounts for approximately 14% of its variations (F = 26.7, r2 = 0.1393, df 1 to 214, P < 0.0001). Patients with DD and ID genotypes showed higher levels of ACR (1.59 +/- 0.2, DD + ID; 0.8 +/- 0.2 mg/mmol, II; P < 0.006 by ANOVA) and bigger LVMI (124.1 +/- 2.3, DD + ID vs. 117.8 +/- 3.6 g/m2, II; P < 0.01 by ANOVA). No differences in the prevalence and degree of target organ damage (TOD) were found when data were analyzed on the basis of the AGT and AT1 genotypes, respectively. Potentially unfavorable combinations of genotypes were also investigated by K-means cluster analysis. Two subgroups of patients were identified (cluster 1, N = 70; cluster 2, N = 57), and each differed significantly with regards to the presence and degree of TOD and patterns of RAAS gene polymorphisms (F, 15.97 for ACR; F, 7.19 for IMT; F, 217.03 for LVMI; F, 3.91 for ACE; F, 4.06 for AGT; and F, 5. 22 for AT1; df 1 to 214, P < 0.02, for each one of the variables examined). CONCLUSION: The D allele of the ACE gene may be an independent risk factor for the development of target organ damage, and evaluating it could be useful for assessing cardiovascular risk in EH. Unfavorable patterns of RAAS genotypes seem to predispose patients to subclinical cardiovascular disease in EH.

Effects of head and neck inclination on bilateral sternocleidomastoid EMG activity in healthy subjects and in patients with myogenic cranio-cervical-mandibular dysfunction.

This study was conducted in order to determine the effect of head and neck position on bilateral electromyographic (EMG) activity of the sternocleidomastoid muscles. The study was performed on 16 patients with myogenic cranio-cervical-mandibular dysfunction (CMD) and 16 healthy subjects. EMG recordings at rest and during swallowing of saliva and maximal voluntary clenching were performed by placing surface electrodes on the right and left sternocleidomastoid muscles. EMG activity was recorded in the left lateral decubitus position, in a darkened room and with the individual's eyes closed, under the following experimental conditions: 1. Head, neck, and body horizontally aligned; 2. Head and neck upwardly inclined with respect to the body, simulating the effect of a thick pillow, 3. Head and neck downwardly inclined with respect to the body, simulating the effect of a thin pillow. Variation of head and neck positions was determined by measuring the distance from the angle of neck and shoulder and the apex of the shoulder (SND = shoulder-neck distance) of each individual. Then, head and neck were forward or downwardly inclined with respect to the body at one-third of SND. A significantly higher contralateral EMG activity and a more asymmetric EMG activity were observed in the CMD group than in the healthy subjects (Kruskal-Wallis Test). These results suggest a different behavior of bilateral sternocleidomastoid EMG activity in CMD patients than in healthy subjects depending on the positioning of the head and neck.

Bilateral lumbar hernia associated with abdominal hernias. A case report.

Multiple abdominal hernias constitute a quite rare event in surgical practice. Lumbar hernias are even rarer and, to our knowledge, this is the first report in the English literature of its association with abdominal hernias. A case of multiple abdominal hernias, namely an epigastric hernia and a left inguinal hernia together with a bilateral lumbar hernia in a 65-year-old man attending the Out-patient department of Hoima Hospital-Uganda is described. A one-stage repair under local anaesthesia was chosen. The patient recovered uneventfully and no recurrence was noted at 1 year follow-up. This case report supports that a "one-stage" procedure under local anaesthesia can be appropriate as surgical treatment of multiple abdominal hernias when abdominal defects are of a small size. A minimal surgical approach to lumbar hernias seems also suitable when transverse muscle aponeurosis defect can be carefully repaired and covered with adjacent muscles.

Blunt splenic rupture--experience in a preserving non-operatively orientated care team in a tropical hospital.

OBJECTIVES: With a view to the prevention of immediate and later complications of splenectomy, especially the risk of overwhelming post-splenectomy sepsis syndrome (OPSS), conservative treatments have been proposed when the haemodynamic condition of the patient permits this. In this study, we present our experience in a preserving non-operatively orientated care team in a tropical hospital. PATIENTS AND METHODS: Twenty patients admitted to Hoima Hospital, Hoima, Uganda with splenic injuries from blunt abdominal trauma between July and December 1995 were included in the study. For every patient, serial monitoring of clinical and haematological data was done. Ultrasonography was used to give an accurate assessment of the severity of splenic and concomitant injuries. In stable patients a conservative approach was adopted. RESULTS: In our study 15 patients were managed non-operatively, while 5 underwent splenectomy. Grades I, II, and IIIa spleen injury was significantly associated with non-operative treatment, while grade V was associated with splenectomy (Student-Newman-Keuls test P < 0.05, Mantel-Haenszel chi-square for trend chi 2 = 8.7, P = 0.003). Comparing the non-operative and laparotomy groups, the length of hospital stay (14.0 v. 12.8 days) was similar (t = 1.71, df 18, P > 0.05), while the average blood transfusion volume given was 1.1 units and 3.0 units respectively (t = 3.58, df 18, P < 0.005). CONCLUSIONS: The present study confirms the ability to preserve an increasing number of traumatised spleens by non-operative therapy. This has become possible as a consequence of increasing experience and confidence in pursuing a non-operative approach based on accurate diagnostic methods. Furthermore, non-operative management does not increase the length of stay in hospital and it reduces the total volume of blood transfusions required. While we agree with others that the choice between operative and non-operative management of splenic trauma should be based mainly on clinical grounds, ultrasonography and peritoneal lavage were important tools in the diagnostic pathway and in decision-making. It is worth noting that a 'safe' grade of spleen injury does not exist, since even minor lesions can lead to massive haemoperitoneum and shock requiring emergency splenectomy. In view of the now well known early and late complications after splenectomy, spleen preservation should be the treatment of choice for splenic trauma, especially in tropical countries.