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PubMed1992

Transvaginal sonography for fetal measurement in early pregnancy.

OBJECTIVE: To establish reference ranges for fetal size by gestation in the first trimester as indicated by cephalic, abdominal and limb measurements using transvaginal sonography. DESIGN: A prospective descriptive study. SETTING: Two antenatal clinics in Milan, Italy. SUBJECTS: 270 women with normal singleton pregnancies at 42-108 days gestation. All had regular cycles and certain dates. INTERVENTIONS: Vaginal ultrasound examination including inspection of fetal structures and lasting 5-15 min. MAIN OUTCOME MEASURES: As many of the following fetal measurements as possible according to gestational age and ease: crown-rump length (CRL), biparietal diameter (BPD), head circumference (HC), abdominal circumference (AC), femur and foot lengths. RESULTS: CRL was measured in 183 fetuses, BPD in 201, HC in 162, AC in 160, femur length in 133 and foot length in 62. The best description of the relation of CRL to gestational age was achieved by a quadratic function (y = -3.98 - 0.308x + 0.0117x2). Mean values thus derived were virtually identical to those obtained by Robinson & Fleming in 1975 with transabdominal static scanning. Fetal BPD, HC, AC and femur length correlated more closely with CRL than gestational age. Reference ranges (mean and 95% data intervals) were constructed for each biometrical measurement in relation to gestational age and CRL. The HC/AC and femur/foot length ratios did not show any significant variation with gestational age or CRL. CONCLUSIONS: These data may be useful in the early detection of genetic disorders affecting the growth of fetal head, trunk and limbs. Genetic and/or environmental variables play an appreciable role in the modulation of early fetal growth.

Abdomen↗

PubMed1996

The KID Study. III: Impact of inpatient rehabilitation on the metabolic control of type I and type II diabetics--a one-year follow-up.

The Kissingen Diabetes Intervention Study (KID) evaluated 1050 diabetic patients of the German Federal Insurance Institution for Salaried Employees (BfA) admitted for inpatient rehabilitation. The data for the prospective longitudinal study (which was collected in a single center) relate to the structure of the patient cohort, socio-economic and psychological factors and the mode of medical management at the time of admission and discharge. Data regarding the same variables was checked by random testing six and twelve months after discharge and used in this part of the study. This cohort of patients is especially interesting for aspects of health policy because it comprises rather young diabetics engaged in highly qualified professional work. Therapy modifications entailing a more intensive insulin regimen were necessary in 20.7% of all type I diabetics. Most of these alterations were maintained over the following 12 months of management by the general practitioner. Improvement of HbA1 levels was related to the number of daily insulin administrations. The results obtained during inpatient treatment in patients on ICT are maintained even one year after their discharge. For type I diabetics, the first training measure especially results in a long-term improvement of the metabolic situation, whereas patients who have already received training several times previously benefit continuously less with increasing repetition of training. After twelve months the intensified insulin therapy of type I diabetics had no further effect on the BMI or the already previously normal serum lipids. In 55.5% of all type II diabetics, the therapy had to be modified. Inpatient rehabilitation resulted in raising the low number of type II diabetics treated just with diet by 5.3%. This proportion was again slightly reduced 12 months later. During inpatient residence the number of overweight type II diabetics treated with drugs was reduced both in the group on oral hypoglycemics and in the group on pre-mixed insulin, according to the weight loss achieved. On the other hand, it was often necessary to intensify the usual insulin regimen twice daily in the group of younger patients with normal body weight. These modifications were maintained twelve months after the stay in hospital for most of these patients. Virtually all type II diabetics on oral hypoglycemics are overweight as a reflection of too early prescriptions of oral hypoglycemics which often neglects the chance of a dietary management only. In this group, therapy modifications were directed towards treatment with diet only and with oral hypoglycemics having an extra-pancreatic action. On metformin, the HbA1 was reduced by 0.3% and the BMI by 0.9 kg/m2 even 12 months later. In the 90% of type II diabetics previously treated with sulphonylureas (almost exclusively glibenclamide), re-modification of therapy from metformin back to the old regimen (16:9%) was especially high. This is probably due to the uncertainty with and general restrictions in the prescription of metformin in the relevant period 1991 to 1995. The results 12 months after inpatient treatment show the small improvement of HbA1 and serum lipids as already seen in other larger interventional studies. The BMI does not change significantly within the relatively short follow-up period. The best long-term results are achieved by a combined therapy with sulphonylurea compounds and metformin. The KID study demonstrates major deficits in intensifying the insulin regimen of type I diabetics and in the individual adaptation to therapy of type II diabetes in Germany, even when younger patients of higher professional status are considered. Interventional inpatient rehabilitation improves their metabolic situation with lasting effect and can compensate deficits in outpatient management by the general practitioner. However, future concepts have to be improved at all levels of diabetic management, with a view to achieving an optimum interaction.

Body Mass Index↗

PubMed2005

Effect of fuels on exercise capacity in muscle phosphoglycerate mutase deficiency.

BACKGROUND: Muscle phosphoglycerate mutase deficiency (PGAMD) is a rare, recessively inherited metabolic myopathy that affects one of the last steps of glycolysis. Clinically, PGAMD resembles muscle phosphorylase deficiency (McArdle disease) and phosphofructokinase deficiency (PFKD). However, it is unknown whether PGAMD is associated with a second-wind phenomenon during exercise, as in McArdle disease, and whether patients with PGAMD, like patients with PFKD and McArdle disease, benefit from supplementation with fuels that bypass the metabolic block. OBJECTIVE: To investigate whether fuels that bypass the metabolic block can improve exercise capacity or whether exercise capacity improves during sustained exercise. DESIGN: Single-blind, placebo-controlled investigation of the effects of glucose, lactate, and intralipid on work capacity in patients with PGAMD. SETTING: National University Hospital, University of Copenhagen, and Neuromuscular Center, Institute for Exercise and Environmental Medicine. Patients Two unrelated men (21 and 26 years old) with PGAMD who since their teens had experienced muscle cramps, muscle pain, and episodes of myoglobinuria provoked by brief vigorous exercise, 4 patients with McArdle disease (mean +/- SD age, 32 +/- 5 years) with 0% residual phosphorylase activity in muscle, and 6 healthy, untrained male volunteers (mean +/- SD age, 23 +/- 1 years) were studied. INTERVENTIONS: Using constant and variable workload protocols on a cycle ergometer, it was investigated whether a spontaneous second wind occurs during exercise in patients with PGAMD, and using a constant workload protocol followed by an incremental load to exhaustion, it was tested whether infusion of lactate, glucose, or intralipid alters the exercise tolerance in PGAMD. MAIN OUTCOME MEASURES: Whether a second wind occurs during exercise and whether fuels that bypass the metabolic block can improve exercise and oxidative capacity. RESULTS: In contrast to patients with McArdle disease, with whom they share many clinical features, in patients with PGAMD, cycle exercise and oxidative capacity are virtually normal, a second wind does not occur, and lipid and lactate supplements do not improve exercise capacity. CONCLUSION: Although the clinical manifestations of PGAMD mimic McArdle disease with respect to the presence of exertional muscle cramps, rhabdomyolysis, and myoglobinuria, this study shows that cycle exercise responses are strikingly different.

Adult↗

PubMedDate not supplied

Fetal obstructive uropathy in trisomy syndromes.

Fetal obstructive uropathy has seldom been described in trisomy syndromes, and its relationship to these syndromes remains unclear. Five trisomic male fetuses, four with trisomy 18 and one with trisomy 21, were identified out of 110 fetuses evaluated for fetal obstructive uropathy. We performed detailed examination on the urinary tracts of four of these fetuses, three with trisomy 18 and one with trisomy 21, following termination in the second trimester. All four had a markedly distended urinary bladder (megacystis), abdominal wall distension, and a small, poorly developed urethra thoughout its full length. All four also had poor development of the prostate with virtual absence of glandular development, as compared to age-matched controls. Posterior urethral valves were not identified in any case. Three of the fetuses (two with trisomy 18 and one with trisomy 21) had unilateral or bilateral hydroureters, and resulting renal tubulocystic or glomerulocystic change. Review of this database reveals an unexpectedly high frequency of trisomies, particularly trisomy 18, suggesting that the relationship may not be coincidental. Abnormal prostate development may be causally related to fetal obstructive uropathies and may be an under-recognized trait in trisomy syndromes. Karyotypic analysis of all fetuses with obstructive uropathy is important since in utero surgical intervention may be contraindicated in cases of fetal aneuploidy.

Chromosomes, Human, Pair 18↗

PubMed2003

[Omega-3 polyunsaturated fatty acids and cardiovascular diseases].

Population studies indicate omega-3 that a high fish intake, such as reported in the early Eskimo and Japanese studies, is associated with a low mortality from coronary heart disease (CHD). These effects have been associated with measurable effects on a series of established and possible risk factors. In most of the later population studies much lower daily intake of fish has been observed, such intake having only small or not even measurable effects on established risk factors. Still, their association with reduced CHD mortality, particularly sudden cardiac death seem to be reasonably well established. Beneficial effects are found at a level of consumption of about 30 g per day or 1 fish meal per week compared with populations rarely or never consuming fish. Such findings are also reflected in studies including analysis of fatty acid composition in adipose tissue and cell membranes. Fish consumption may be a marker for a healthier lifestyle or, alternatively, fish consumers may be at higher self-perceived risk for CHD and are therefore eating fish to reduce their high baseline risk. Despite all these limitations, the population studies seem to indicate that a high fish intake is associated with a low mortality from CHD. GISSI-Prevenzione was conceived as a population, pragmatic trial on patients with recent myocardial infarction and it was conducted in the framework of the Italian public health system. In GISSI-Prevenzione, 11,323 patients were enrolled in a clinical trial aimed at testing the effectiveness of omega-3 PUFA and vitamin E. Patients were invited to follow Mediterranean dietary habits, and were treated with up-to-date preventive pharmacological interventions. Long-term omega-3 PUFA 1 g daily, but not vitamin E 300 mg daily, was beneficial for death and for combined death, non-fatal myocardial infarction, and stroke. All the benefit, however, was attributable to the decrease in risk for overall, cardiovascular, cardiac, coronary, and sudden death. In GISSI-Prevenzione, long-term administration of omega-3 PUFA (1 g daily) significantly decreased the risk of overall (-20%), cardiovascular (-30%), and sudden death (-45%). At variance from the orientation of a scientific scenario largely dominated by the "cholesterol-heart hypothesis", GISSI-Prevenzione results indicate omega-3 PUFA (virtually devoid of any cholesterol-lowering effect) as a relevant pharmacological treatment for secondary prevention after myocardial infarction.

Clinical Trials as Topic↗

PubMed1981

Role of phagocytic cells in cancer.

Partial manifestations of the anti-tumor defence in the organism will sometimes lead to surprising changes in the clinical picture of the disease. This must be taken into consideration and, if possible, such therapeutical procedures must be chosen which do not interfere with the course of defence reactions. Therefore, the study of the organism's anti-tumor defence mechanisms is of theoretical as well as of practical value. In Hodgkin's disease a significant increase in phagocytic activity could be observed when the disease was in progress; during clinical remission the values returned to normal ones [181]. The phagocytic activity may be supposed to reflect the dynamic situation between the host and the tumor in man [196]. The determination of phagocytic activity may be useful as an indicator of the extent or activity of the disease [181]. Phagocytic function may be affected by a surgical intervention [46], radiotherapy [179, 183] and by anti-tumor chemotherapy [3, 209]. On stimulating MPS during the course of radiotherapy, improved clinical results have been observed [115]. When examining patients in the course of treatment and after it, a need was felt for methods that can easily be applied and that enable the state of the defence capacity of the organism to be taken into account. The measurement of the phagocytic activity of MPS in clinical practice by using the 131I labelled aggregated human albumin [115] can only be used at selected workplaces. Today, however, drugs and therapeutical procedures with immunosuppressive effects are virtually used in all workplaces where there are patients with malignant tumors. Therefore, an original method of phagocytosis of latex particles in vitro has been elaborated. This method is primarily aimed at orientation, but it may be employed in every hematological laboratory. It determines the intensity of phagocytic activity of leukocytes. The differences between the values obtained in cancer and those obtained in healthy subjects and patients with non-malignant disorders are highly significant. This statement has been made on the basis of 363 examinations performed in clinically healthy subjects, in patients with cancer and in patients with non-malignant disorders. The results were analyzed statistically and it has been found out that the phagocytic capacity of leukocytes is significantly activated in the presence of a pathological process in the organism. This activation is mush more evident in cancer patients than in patients with non-malignant disorders. Strikingly low values were observed in the terminal stage of the disease when the defence capacity of the organism has broken down. These findings induced us to consider the suitability of this kind of examination. It can be used alone or in combination with other methods for estimating the defence capacity of the organism, or for choosing the right therapeutical measures...

Anaerobiosis↗

PubMed2001

Outcomes from television sets toppling onto toddlers.

OBJECTIVE: To assess outcomes of trauma caused by television sets falling onto children. METHODS: Retrospective review of medical charts of 183 children aged 7 years and younger hospitalized for injuries caused by falling television sets. Descriptive statistics were applied. DATA SOURCES: Phase 2 (1988-1995) and phase 3 (1995-1999) of the National Pediatric Trauma Registry. OUTCOME MEASURES: Demographics, injured body region, injury severity measured by the Injury Severity Score, length of hospital stay, admission to the intensive care unit, surgical intervention, in-hospital death rate, disability resulting from the injury, and disposition at discharge from the hospital. RESULTS: The sample population represented 0.5% of all National Pediatric Trauma Registry admissions in this age group. More than half (57.4%) of the children were boys, and more than three quarters (76.0%) were 1 to 4 years of age. In most cases (95.1%), the injury occurred at home. Most children (68.3%) sustained head injury, and 43.7% sustained injuries to multiple body regions. More than a quarter (28.4%) of the children had injuries of moderate to critical severity (Injury Severity Score, 10-75), about a third (31.1%) required admission to the intensive care unit, and 20.2% needed 1 or more surgical interventions. The average length of hospitalization was 3.3 days. Five children (2.7%) died, and 48 (26.2%) developed functional limitations, which required discharge to a rehabilitation facility in 5 cases. Most (94.0%) of the children returned to their home. The proportion of television set-related injuries increased more than 100% during the study period. CONCLUSIONS: The injuries reported are not trivial. Not only did they require hospitalization, but they also resulted in an in-hospital death rate comparable to the 2.5% rate observed in children of the same age group injured by unintentional blunt trauma, inclusive of motor vehicle traffic-related injuries. Since virtually all American children are at risk for such injury, we suggest that television set designs be modified to reduce the incidence and severity of the problem.

Accidents, Home↗

PubMed2005

Surrogate markers for atherosclerotic disease.

PURPOSE OF REVIEW: Novel treatment modalities for cardiovascular prevention are emerging rapidly. Since it is virtually impossible to evaluate all these new compounds in long-term trials using clinical end points, there is an urgent need for validated surrogate markers of atherosclerosis to save both time and costs. Over the last decade, the use of imaging markers has been widely introduced into drug-development strategies. Here we will discuss the most commonly used techniques. RECENT FINDINGS: Whereas both testing of endothelial function, assessed as flow-mediated dilation, and assessment of carotid intima-media thickness have been shown to predict future cardiovascular events, predominantly intima-media thickness has been used successfully as a surrogate marker in intervention studies. More recently, standardization of intravascular ultrasound has also enabled reproducible assessment of coronary atheroma volume. Multidetector computed tomography and electron-beam computed tomography have proven useful in providing quantitative information on plaque burden and coronary calcium content, respectively. Although cardiovascular magnetic resonance (CMR) is improving continuously, additional technical improvements will be mandatory before this technique can be implemented in multicenter clinical studies. SUMMARY: The imaging modalities reviewed here all provide specific information on either functionality or morphology of the vasculature. The value of carotid intima-media thickness for cardiovascular risk prediction has been studied most extensively. Whereas assessment of plaque burden using intravascular ultrasound appears to be the most direct way to quantify coronary changes, its predictive value for future cardiovascular events remains to be established. Awaiting further technical improvements, CMR is expected to provide the most valuable information for the evaluation of atherosclerosis in the near future.

Arteriosclerosis↗

PubMedDate not supplied

Laparoscopic interventions in the gut: yesterday, today, and tomorrow.

The development of laparoscopic interventional surgery has brought about a revolution in general surgery over the past 5 years. Laparoscopic cholecystectomy has now become the treatment of choice for symptomatic cholelithiasis because of a reduction in access trauma, resulting in less postoperative pain and a faster recovery. Laparoscopic fundoplication for gastroeosophageal reflux also looks to be a promising procedure which will probably become generally accepted. Laparoscopic hernia repair, although widely practised, has raised question marks because of doubt about recurrence rates and major complications such as intestinal obstruction. Laparoscopic colectomy has similarly raised concerns about complication rates and tumour recurrence rates. Laparoscopic appendicectomy offers marginal benefits over open appendicectomy. Virtually every other intra-abdominal procedure has been performed laparoscopically, but most require further evaluation.

Cholecystectomy, Laparoscopic↗

PubMed2004

Hepatic resection for colorectal metastases - a national perspective.

BACKGROUND: Many consultant surgeons are uncertain about peri-operative assessment and postoperative follow-up of patients for colorectal liver metastases, and indications for referral for hepatic resection. The aim of this study was to assess the views the consultant surgeons who manage these patients. METHODS: A postal questionnaire was sent to all consultant members of the Association of Coloproctology of Great Britain and Ireland and of the Association of Upper Gastrointestinal Surgeons of Great Britain and Ireland. The questionnaire assessed current practice for preoperative assessment and follow-up of patients with colorectal malignancy and timing of and criteria for hepatic resection of metastases. Number of referrals/resections were also assessed. RESULTS: The response rate was 47%. Half of the consultants held joint clinics with an oncologist and 89% assessed the liver for secondaries prior to colorectal resection. Ultrasound was used by 75%. Whilst 99% would consider referring a patient with a solitary liver metastasis for resection, only 62% would consider resection for more than 3 unilobar metastases. The majority (83%) thought resections should be performed within the 6 months following colorectal resection. During follow-up, 52% requested blood CEA levels and 72% liver ultrasound. Half would consider chemotherapy prior to liver resection and 76% performed at least one hepatic resection per year with a median number of 2 resections each year. CONCLUSIONS: A substantial proportion of patients are assessed for colorectal liver metastases preoperatively and during follow-up though there is spectrum of frequency of assessment and modality for imaging. Virtually all patients with solitary hepatic metastases are considered for liver resection. Patients with more than one metastasis are likely to be not considered for resection. Many surgeons are carrying out less than 3 resections each year.

Attitude of Health Personnel↗

PubMed1988

The presence of counsel at forensic psychiatric examinations.

In virtually all situations involving forensic psychiatric assessments, the patient is represented by counsel. But does this fact entitle the lawyer to be present at the clinical evaluation? In a series of New York cases spanning a generation, judges have allowed presence of counsel at the psychiatric examination. The most common reason given for such a conclusion is to assure better cross-examination of the expert witness. Psychiatric evaluations mandated by law necessitate several guidelines different from those of the usual doctor/patient relationship. While we may have to accept the presence of attorneys in our consulting rooms, they should be observers only. To allow active intervention would distort the clinical process.

Commitment of Persons with Psychiatric Disorders↗

PubMed1994

The effect of neuromuscular blockade on human fetal heart rate and its variation.

OBJECTIVE: To determine the effect of neuromuscular blockade on fetal heart rate and its variation. DESIGN: Case control study. SETTING: Tertiary referral fetal medicine unit in a London teaching hospital. SUBJECTS: Forty women with rhesus iso-immunisation requiring an intravascular fetal blood transfusion between 28 and 34 weeks gestation. INTERVENTION: Intravascular injection of pancuronium to the fetus prior to fetal blood transfusion in 20 cases. MAIN OUTCOME MEASURES: Comparison between the group receiving pancuronium and the control group with regard to differences in perceived fetal activity and computer derived numerical indices of fetal heart rate and fetal heart rate variation after fetal blood transfusion. RESULTS: After transfusion in the control group, there were fewer perceived fetal movements, a small reduction in fetal heart rate but no differences in number of fetal heart rate accelerations or measures of fetal heart rate variation. In the study group, pancuronium produced no change in fetal heart rate despite a virtual abolition of perceived fetal movements and fetal heart rate accelerations. Measures of fetal heart rate variation were reduced by 60%. Comparison of the pre- to post-transfusion changes between the two groups showed significant differences for all fetal heart rate indices. CONCLUSION: Fetal activity accounts for more than half the measured variation of the human fetal heart rate.

Blood Transfusion, Intrauterine↗

PubMed1999

[Familial alcohol abuse in the context of sexual and physical abuse offenses by male adolescents and young adults].

This study investigated whether and to what extent defined samples of young male offenders (sexual and assault offences) differ with regard to the effects of alcohol abuse in their families. Thirty-eight young men had sexually assaulted women of their own age or older, 36 subjects had sexually abused children and 33 had committed assault offences. The incidence of alcohol abuse of mothers was the same in all groups. The alcohol abuse of fathers was most common in the group of assault offences and least common in the group of sexual offences against women of the same age or older. In contrast, alcohol abuse of the delinquent young men after the age of 14 years and the influence of alcohol at the time of offence were virtually identical in the group of sexual offences against women and assault offences, whereas alcohol abuse and the influence of alcohol at the time of offence were only rarely observed among the sexual offences against children. Analysis of alcohol abuse and violence in the intrafamilial context revealed a different and possibly specific profile for each group: Paternal alcohol abuse was associated with alcohol abuse of the son (sexual offences, women victims), with expulsion from school (sexual offences, child victims), and with the influence of alcohol at the time of offence (assault-offences). Such profiles may be helpful in the assessment of the offence and in interventions aimed at preventing relapse: with regard to the degree of alcohol abuse, with regard to the respective delinquent development and with regard to the interaction of the two disorders.

Adolescent↗

PubMedDate not supplied

[Risk factors for the progression of chronic kidney failure].

Virtually all renal diseases progress, although at different rates, to end-stage renal failure. The main clinical factors which may explain such relentless progression are reviewed and include: the underlying renal pathology, with the most rapid progression rate observed in glomerular disease and in polycystic kidney disease; systemic hypertension, a significant risk factor for progression in any renal disease; the magnitude and duration of proteinuria with the fastest progression rate found in the nephrotic syndrome; the degree of functional renal deterioration at which so called conservative treatment is prescribed. The proper identification of these risk factors may result in rational dietary and non-dietary intervention with the aim of slowing the progression of chronic renal disease.

Humans↗

PubMed2002

New developments in anti-HIV chemotherapy.

Virtually all the compounds that are currently used, or are subject of advanced clinical trials, for the treatment of human immunodeficiency virus (HIV) infections, belong to one of the following classes: (i) nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs): i.e. zidovudine (AZT), didanosine (ddI), zalcitabine (ddC), stavudine (d4T), lamivudine (3TC), abacavir (ABC), emtricitabine [(-)FTC], tenofovir disoproxil fumarate; (ii) non-nucleoside reverse transcriptase inhibitors (NNRTIs): i.e. nevirapine, delavirdine, efavirenz, emivirine; and (iii) protease inhibitors (PIs): i.e. saquinavir, ritonavir, indinavir, nelfinavir, amprenavir and lopinavir. In addition to the reverse transcriptase (RT) and protease reaction, various other events in the HIV replicative cycle can be considered as potential targets for chemotherapeutic intervention: (i) viral adsorption, through binding to the viral envelope glycoprotein gp120 (polysulfates, polysulfonates, polycarboxylates, polyoxometalates, polynucleotides, and negatively charged albumins); (ii) viral entry, through blockade of the viral coreceptors CXCR4 [bicyclam (AMD3100) derivatives] and CCR5 (TAK-779 derivatives); (iii) virus-cell fusion, through binding to the viral envelope glycoprotein gp41 (T-20, T-1249); (iv) viral assembly and disassembly, through NCp7 zinc finger-targeted agents [2,2'-dithiobisbenzamides (DIBAs), azadicarbonamide (ADA)]; (v) proviral DNA integration, through integrase inhibitors such as 4-aryl-2,4-dioxobutanoic acid derivatives; (vi) viral mRNA transcription, through inhibitors of the transcription (transactivation) process (flavopiridol, fluoroquinolones). Also, various new NRTIs, NNRTIs and PIs have been developed that possess, respectively: (i) improved metabolic characteristics (i.e. phosphoramidate and cyclosaligenyl pronucleotides by-passing the first phosphorylation step of the NRTIs), (ii) increased activity ["second" or "third" generation NNRTIs (i.e. TMC-125, DPC-083)] against those HIV strains that are resistant to the "first" generation NNRTIs, or (iii) as in the case of PIs, a different, nonpeptidic scaffold [i.e. cyclic urea (mozenavir), 4-hydroxy-2-pyrone (tipranavir)]. Nonpeptidic PIs may be expected to inhibit HIV mutant strains that have become resistant to peptidomimetic PIs. Given the multitude of molecular targets with which anti-HIV agents can interact, one should be cautious in extrapolating the mode of action of these agents from cell-free enzymatic assays to intact cells. Two examples in point are L-chicoric acid and the nonapeptoid CGP64222, which were initially described as an integrase inhibitor or Tat antagonist, respectively, but later shown to primarily act as virus adsorption/entry inhibitors, the latter through blockade of CXCR4.

Anti-HIV Agents↗

PubMed1995

Rheumatic fever and poststreptococcal reactive arthritis.

Rheumatic fever is a catastrophic illness in many parts of the world, particularly in developing nations, where the incidence has been estimated to be between 10 and 15 million new cases each year. In the United States, rheumatic fever had become a rarity, having virtually disappeared by the mid 1960s. Of increasing concern, however, was the abrupt rise in the incidence of rheumatic fever in the United States in the mid 1980s, with reported "outbreaks" in middle-class communities in five cities and two military camps. Recently, a number of cases of poststreptococcal reactive arthritis have been reported. On close examination, however, these are most likely alternate clinical presentations of rheumatic fever. It is widely accepted that rheumatic fever occurs following an overactive immune response by a genetically susceptible host to oropharyngeal infection with group A beta-hemolytic streptococci. Nevertheless, details of pathogenesis at a level allowing more effective intervention remain obscure. The question of pathogenesis holds a deep interest, because rheumatic fever is one of the few autoimmune diseases with a known infectious etiology.

Adult↗

PubMed1985

The pericardial hypothesis: a mechanism of acute shifts of the left ventricular diastolic pressure-volume relation.

Changes in LV diastolic P-V relations may be caused by changes in myocardial distensibility and by changes in extraventricular constraint. Experimental studies suggest that the upward shift of the LV diastolic P-V relation associated with pacing tachycardia, in patients with angina pectoris, is due to decreased myocardial distensibility which possibly represents incomplete relaxation. However, shifts in the LV diastolic P-V relation with vasodilator and vasoconstrictor agents seem to be caused by changes in extraventricular constraint. Experimental and clinical data show that such interventions do not significantly change the LV transmural P-V relation. This supports the hypothesis that these shifts are due to changes in pericardial pressure. Our data suggest that such vasoactive agents act by shifting blood between the (splanchnic) venous compartment and the heart, thereby changing heart size and in turn pericardial pressure. These concepts have significantly improved our understanding of the mechanisms of action of vasoactive agents. It seemed a paradox that vasodilators (e.g., nitroglycerine) could substantially lower filling pressure of the failing left ventricle without reducing cardiac output. Because of the downward-shift in the P-V relation with nitroglycerine, preload is virtually unchanged and therefore stroke volume is maintained. Appreciation of these phenomena has considerable impact on how haemodynamic measurements are interpreted. It is obvious that the use of LV end-diastolic pressure as an index of end-diastolic volume may lead to serious misinterpretations of ventricular function. Our demonstration that right atrial pressure might be used to assess pericardial pressure provides a potentially useful way to estimate LV transmural pressure, and therefore an accurate measure of preload.

Animals↗

PubMed2001

Postchallenge hyperglycemia in a national sample of U.S. adults with type 2 diabetes.

OBJECTIVE: Postchallenge hyperglycemia (PCH) is known to contribute to suboptimal glycemic control in adults with non-insulin-requiring type 2 diabetes. The objective of this study was to estimate the prevalence of PCH among individuals with diabetes. RESEARCH DESIGN AND METHODS: We conducted a cross-sectional analysis of data from the Third National Health and Nutrition Examination Survey (1988-1994) in adults aged 40-74 years with diabetes who were not using insulin (i.e., they used oral hypoglycemics or received no pharmacological therapy). Each respondent underwent a standard 75-g oral glucose tolerance test. PCH was defined as a 2-h glucose level >or=200 mg/dl. RESULTS: Overall, PCH was present in 74% of those with diagnosed diabetes. Although it was present in virtually all (99%) of the diabetic adults under suboptimal glycemic control (HbA(1c) >or=7.0%), PCH was also common (39%) among those under optimal control (HbA(1c) <7.0%). Likewise, among sulfonylurea users, PCH was present in 99% of those under suboptimal control and in 63% of those under good control. Similar patterns were observed in those with undiagnosed diabetes. Isolated PCH (2-h glucose >or=200 mg/dl and fasting glucose <126 mg/dl) was present in 9.8% of the adults with diagnosed diabetes. CONCLUSIONS: These data suggest that PCH is common among diabetic adults in the U.S., even in the setting of "optimal" glycemic control and sulfonylurea use. Interventions designed to lower postprandial glucose excursions may help improve overall glycemic control in the general population of U.S. adults with diabetes.

Adult↗