Tolerability of four-drug antiretroviral combination therapy in primary HIV-1 infection.

OBJECTIVES: Rapid initiation of antiretroviral therapy (ART) is important for individuals with high baseline viral loads, such as in primary HIV-1 infection (PHI). Four-drug regimens are sometimes considered; however, data are lacking on tolerability. We aimed to evaluate the tolerability of four-drug regimens used in the Research in Viral Eradication of HIV-1 Reservoirs (RIVER) study. METHODS: At enrolment, ART-naïve adult participants or those newly commenced on ART were initiated or intensified to four-drug regimens within 4 weeks of PHI. Rapid start was defined as pre-confirmation or ≤ 7 days of confirmed diagnosis. Primary and secondary outcomes were patient-reported adherence measured by 7-day recall and regimen switches between enrolment and randomization, respectively. RESULTS: Overall, 54 men were included: 72.2% were of white ethnicity, with a median age of 32 years old, 42.6% had a viral load of ≥ 100 000 HIV-1 RNA copies/mL, and in 92.6% sex with men was the mode of acquisition of HIV-1. Twenty (37%) started a four-drug regimen and 34 (63%) were intensified. Rapid ART initiation occurred in 28%, 100% started in ≤ 4 weeks. By weeks 4, 12, and 24, 37.0%, 69.0%, and 94.0% were undetectable (viral load < 50 copies/mL), respectively. Adherence rates of 100% at weeks 4, 12, 22 and 24 were reported in 88.9%, 87.0%, 82.4% and 94.1% of participants, respectively. Five individuals switched to three drugs, four changed their regimen constituents, and two switched post-randomization. CONCLUSIONS: Overall, four-drug regimens were well tolerated and had high levels of adherence. Whilst their benefit over three-drug regimens is lacking, our findings should provide reassurance if a temporarily intensified regimen is clinically indicated to help facilitate treatment.

Comparative values of the precordial and transesophageal approaches in the echocardiographic evaluation of atrial baffle function after an atrial correction procedure.

Previous methods used to assess atrial baffle function after correction of transposition of the great arteries have included precordial echocardiography and cardiac catheterization. To evaluate whether single plane transesophageal echocardiography might provide additional information, its findings were correlated with information derived from both precordial echocardiography and cardiac catheterization in 15 patients (14 Mustard procedures, 1 Senning procedure) aged 4.2 to 33 years (mean 16.3). Precordial ultrasound with combined imaging, color flow mapping and pulsed Doppler ultrasound visualized the supramitral portion of the common systemic venous atrium in every case but could identify only superior limb obstruction in three of six patients, mid-baffle obstruction in zero of two and inferior limb obstruction in zero of two patients. Transesophageal studies with use of the same range of ultrasound methods demonstrated superior limb obstruction (severe in four, mild in two) in six of six patients, mid-baffle obstruction in two of two and inferior limb obstruction in two of two patients. The entire pulmonary venous atrium was equally well interrogated by either ultrasound approach, with both identifying three cases (two mild, one moderate) of mid-pulmonary venous atrium obstruction. However, individual pulmonary vein velocity profiles could only be recorded by transesophageal pulsed Doppler ultrasound. Precordial studies identified baffle leaks (1 large, 2 small) in only three patients, whereas transesophageal studies identified 11 such baffle leaks (1 large, 10 small), which were multiple in two patients. It is concluded that transesophageal echocardiography provides a more detailed and accurate assessment of atrial baffle morphology and function than is provided by either precordial ultrasound or cardiac catheterization.(ABSTRACT TRUNCATED AT 250 WORDS)

Addendum to the IPEMB code of practice for the determination of absorbed dose for x-rays below 300 kV generating potential (0.035 mm Al-4 mm Cu HVL).

This addendum to the code of practice for the determination of absorbed dose for x-rays below 300 kV has recently been approved by the IPEM and introduces three main changes: (i) Due to a lack of available data the original code recommended a value of unity for k(ch) in the very-low-energy range (0.035-1.0 mm Al HVL). A single table of k(ch) values, ranging from 1.01 to 1.07, applicable to both designated chamber types is now presented. (ii) For medium-energy x-rays (0.5-4 mm Cu HVL) methods are given to determine the absorbed dose to water either at 2 cm depth or at the surface of a phantom depending on clinical needs. Determination of the dose at the phantom surface is derived from an in-air measurement and by extending the low-energy range up to 4 mm Cu HVL. Relevant backscatter factors and ratios of mass energy absorption coefficients are given in the addendum. (iii) Relative dosimetry: although not normally forming part of a dosimetry code of practice a brief review of the current literature on this topic has been added as an appendix. This encompasses advice on techniques for measuring depth doses, applicator factors for small field sizes, dose fall off with increasing SSD and choice of appropriate phantom materials and ionization chambers.

Hemopoietic stem cell inhibitor (SCI/MIP-1 alpha) also inhibits clonogenic epidermal keratinocyte proliferation.

The maintenance and regulation of continuously renewing tissues is ultimately controlled at the level of stem-cell proliferation. We have recently identified a reversible inhibitor of hemopoietic stem-cell proliferation (stem-cell inhibitor [SCI]), which is identical to the macrophage inflammatory protein, MIP-1 alpha, a 69-amino-acid heparin-binding cytokine. To test the cell/tissue specificity of the inhibition of proliferation by SCI/MIP-1 alpha, we have investigated its activity on epidermal keratinocytes, the principal cell type of another continuously renewing tissue. Here we show that SCI/MIP-1 alpha inhibits the proliferation of epidermal keratinocytes in vitro and that the MIP-1 alpha mRNA is present in epidermal Langerhans cells but not in keratinocytes. This suggests an important growth regulatory function for SCI/MIP-1 alpha in keratopoiesis, as well as hemopoiesis, and may also indicate a novel role for the epidermal Langerhans cell. As SCI/MIP-1 alpha can inhibit the proliferation of embryologically distinct precursor cells, this raises the possibility that it may also function in a number of other tissues.

Transthoracic three-dimensional echocardiography in the preoperative assessment of atrioventricular septal defect morphology.

A prospective study of 3-dimensional (3-D) transthoracic echocardiographic definition of atrioventricular septal defect (AVSD) morphology and its dynamic changes during the cardiac cycle was performed. The information obtained from 2-D and 3-D transthoracic echocardiography (TTE) was compared with intraoperative findings in an unselected group of 15 patients with AVSD (median age 22 months). In all study patients, 3-D reconstructions provided anatomic views of the atrioventricular valve(s) en face from either atrial or ventricular perspectives that allowed comprehensive assessment of dynamic valve morphology and the mechanism of valve reflux. Left-sided valve function was correctly assessed by 2-D TTE in 11 of 15 patients (73%) and in 14 of 15 (93%) by 3-D TTE. In 6 of 15 patients (40%), the severity of right-sided valve reflux was described precisely by 2-D TTE and in 12 of 15 patients (80%) by 3-D TTE. Additionally, 3-D TTE supplemented the diagnostic information to that available from 2-D TTE on atrial and ventricular septal defects. Although primum atrial septal defects were depicted by 2-D and 3-D TTE in all 15 patients, the description of defect size was more precise by the 3-D TTE (80% vs. 100%, respectively). The presence of secundum atrial septal defect was correctly diagnosed by both TTE techniques in 10 of 15 patients. Disagreement regarding the size of the defect was present only in 2 of 10 patients by 2-D TTE. In another 2 patients, 3-D TTE described multiple defect fenestrations that were missed by 2-D TTE. Thus, the agreement score was 73% for 2-D and 100% for 3-D echo. The agreement for the presence and sizing of ventricular septal defects was 67% for 2-D and 93% for 3-D echo. We conclude that 3-D TTE provided accurate anatomic reconstructions of the common atrioventricular junction and that the use of dynamic 3-D TTE enhanced the anatomic diagnostic capability of standard 2-D TTE. Medica, Inc.

Oncocytic cardiomyopathy in an infant with oncocytosis in exocrine and endocrine glands.

An 11 week old female infant with congenitally malformed eyes died from intractable cardiac arrhythmia. The heart showed extensive oncocytic transformation of myocytes, and this distinctive cardiomyopathy affected the conduction system. Oncocytes were found also in endocrine (pituitary, thyroid) and exocrine (submandibular, sublingual, minor salivary) glands. There is morphologic evidence that the lesions were caused early in gestation, possibly by a viral infection such as rubella.

Subclavian flap repair of coarctation of the aorta in neonates. Realization of growth potential?

The subclavian flap repair for coarctation of the aorta allows potential for growth by utilizing autogenous tissue. Although well documented in young children, its promise in the tiny neonate warrants further evaluation. Since August, 1979, 29 patients, including 24 infants, have undergone subclavian flap repair at the University of Maryland Hospital. Weights ranged from 1.4 to 5 kg (mean 3.2 kg). All patients less than 6 months old had associated intracardiac defects and were in severe congestive failure. Fifteen responded to preoperative prostaglandin infusions. The overall early mortality was 14%; among the neonates it was 21%; and among those operated upon within the first week of life, 33%. There was one intraoperative death among the eight patients who underwent simultaneous pulmonary artery banding. There were no deaths among patients older than 5 days at operation. Four of the five neonates who died had some variant of hypoplastic left heart syndrome, with severe stenosis or atresia of the systemic atrioventricular valve, critical aortic stenosis, or hypoplastic left ventricle. Twenty-two survivors continue to do well up to 3.7 years postoperatively (mean follow-up 26 months). At follow-up all patients are normotensive with brisk lower extremity pulses. Patients now weigh 1.3 to 6.9 (mean 2.3) times their operative weight, and only one patient has a measured arm-to-leg gradient greater than 10 mm Hg (mean gradient 3.7 mm Hg). Seven of the neonates have undergone repeat catheterization, and all had satisfactory growth of the subclavian flap segment of repair and no gradient. Two older patients (3 and 4 years old at operation) have undergone exercise testing 3.7 years after repair, with peak exercise gradients of only 7 and 15 mm Hg. We therefore continue to utilize this technique for the treatment of coarctation even in tiny neonates.

The biochemical consequences of cardiopulmonary bypass surgery in children.

The changes in serum enzyme activities after successful and uncomplicated cardiopulmonary bypass (CPB) surgery in children are described. After maximum serum enzyme activities were attained, they thereafter declined steadily without any secondary peaks of activity, to be at or near normal activities by the seventh day after surgery. The possible sources and mechanisms of enzyme leakage from tissues after CPB are discussed. The concentration of some physiologically important constituents were determined in pump prime fluids and in the common circulation on bypass. The consequences of haemodilution on small children were undesirably reduced concentrations of magnesium, calcium and albumin, and this state persisted for some days after the end of bypass. Some possible implications of such unphysiological pump primes are discussed. We suggest that ASp AT, Ala AT, CK-MB, magnesium, calcium and urea should be routinely monitored for the first four days after surgery.

Absorbed-dose calibrations in high-energy photon beams at the National Physical Laboratory: conversion procedure.

The absorbed-dose calibration service from NPL is based on a primary-standard calorimeter that measures absorbed dose to graphite. Secondary-standard dosemeters are calibrated in absorbed dose to water in a 60Co gamma-ray beam and in x-ray beams over a range of generating potentials from 4 MV to 19 MV. Two methods were used to convert the calibrations of working-standard ionization chambers from absorbed dose to graphite into absorbed dose to water. One method involved the use of published interaction data for photons and secondary electrons, and required a knowledge of the chamber construction. The second method involved the calculation of the ratio of absorbed dose in graphite and water phantoms irradiated consecutively in the same photon beam using the photon-fluence scaling theorem. The two methods were in agreement to 0.1%.

Radiographic exposure slide rules.

Before automatic exposure control was fitted to diagnostic X-ray sets, radiographers were faced with the problem of choosing the parameters that would give the best radiographic image. For a new X-ray set whose performance was unknown, this was no easy matter, and often required considerable trial and error because of the number of variables involved. To reduce the amount of work, special slide rules were invented which calculated the effect of some of these variables. Five such slide rules, dating from between about 1910 and 1950, are illustrated and discussed, including the light they shed on changes in radiographic practice over the years.

Comparison of five clinical weaning indices.

BACKGROUND: Despite extensive data acquired in the area of weaning, clinicians still struggle with the questions of how and when to begin the process. Clinical weaning indices, designed to predict weaning potential, are often difficult to use. They provide an answer at a specific time; extrapolation to the weaning process is rarely possible. No single index has proven to be superior. OBJECTIVES: To test the efficacy of five clinical weaning indices (Burns Weaning Assessment Program; Weaning Index; frequency tidal volume ratio; compliance, resistance, oxygenation and pressure index; and negative inspiratory pressure) at regular intervals during withdrawal of ventilatory support and to determine threshold levels for the program. METHODS: A prospective convenience sample consisted of 37 adult critical care patients requiring mechanical ventilation for at least 7 days and identified as stable and ready to wean. Data were collected on all weaning indices every other day until the patient was weaned. RESULTS: With the exception of the Burns Weaning Assessment Program, weaning indices did not change significantly from preweaning scores. Furthermore, the results failed to demonstrate that any of the five clinical weaning indices have strong predictive power related to weaning trial outcomes, although all the indices had negative predictive values that may be helpful in predicting unsuccessful weaning trials. CONCLUSIONS: The results of this study suggest that the process of weaning may be enhanced by comprehensive, systematic approaches and that clinical weaning indices like the Burns Weaning Assessment Program might best serve as tools to track trends in progress, keep care planning on target, and prevent unsuccessful weaning trials.

Effect of body position on spontaneous respiratory rate and tidal volume in patients with obesity, abdominal distension and ascites.

BACKGROUND: Nursing textbooks and tradition suggest that the high-Fowler's position is best to optimize diaphragmatic excursion and effective breathing pattern. The optimal position for intubated patients with obesity, ascites or abdominal distention has yet to be determined but is important because weaning trial outcomes may reflect the effect of position rather than weaning trial tolerance. OBJECTIVE: To determine the body position that optimizes breathing pattern (tidal volume and respiratory rate) in spontaneously breathing, intubated patients with a large abdomen. METHODS: Nineteen intubated patients with abdominal distention, ascites or obesity who were on continuous positive airway pressure or the pressure support ventilation mode were studied in the 0 degrees, 45 degrees, 90 degrees and reverse Trendelenburg's at 45 degrees positions for 5 minutes prior to data collection. RESULTS: The RT at 45 degrees position resulted in a significantly larger tidal volume and lower respiratory rate than the 90 degrees position in intubated, spontaneously breathing patients with a large abdomen. The 45 degrees position resulted in a significantly lower respiratory rate than at 90 degrees; however, no difference in tidal volume was demonstrated. DISCUSSION: A high respiratory rate and low tidal volume potentiates atelectasis and ultimately failure to wean. It is important that the effect of positioning on breathing pattern in intubated patients be determined so that care planning results in optimal outcomes. CONCLUSIONS: The results of this study have implications for the selection of chair and bed positioning during weaning trials.

Comparison of nasogastric tube securing methods and tube types in medical intensive care patients.

BACKGROUND: Nasogastric tube displacement can result in serious complications such as aspiration and inadvertent migration of the tube into the lungs. Replacement of the tubes is costly, time- and effort-intensive, uncomfortable for the patients, and potentially dangerous. OBJECTIVE: To determine the best of three methods for securing nasogastric tubes in a medical intensive care population and to identify variables related to the failure of tube securing methods. METHODS: A convenience sample of 103 patients requiring duodenal or standard gastric tubes for feeding, medication delivery, or decompression were randomly assigned to one of three taping methods: pink tape, clear tape, or "butterfly," for a total of 264 taping episodes. Data collection included the mean time until failure of the securing methods as well as variables such as patient alertness and mobility. RESULTS: The mean time until failure was 100 hours with pink tape versus 56 hours with clear tape and 30 hours with the "butterfly." Differences were significant. Duodenal tubes stayed secured longer than standard sump tubes (mean time until failure was 86 vs 41 hours) for all taping methods, but not significant relationship was demonstrated between mean time until failure and variables such as alertness, sedation, confusion, mobility, and the use of restraints. CONCLUSION: Our results showed that the pink tape method was superior. Nasogastric tube securing methods in adult critical care patients vary in efficacy and should be selected carefully.

Design, testing, and results of an outcomes-managed approach to patients requiring prolonged mechanical ventilation.

BACKGROUND: Outcomes management that uses critical pathways may decrease costs while improving outcomes for patients who require prolonged mechanical ventilation. OBJECTIVE: To study the efficacy of an outcomes-managed approach to weaning patients from prolonged (more than 3 days) mechanical ventilation. METHODS: A method of multidisciplinary care delivery was designed that included an outcomes manager, a care pathway for patients receiving mechanical ventilation, and weaning protocols. Data collection consisted of three parts: a retrospective review of 124 patients who required prolonged ventilation during a 1-year period before implementation of the care model, a 6-month prospective study in which 91 patients were alternately assigned by month to an outcomes-managed approach or a non-outcomes-managed approach, and a 6-month prospective study of 90 patients in which an outcomes-managed approach without alternate-month assignment was used. RESULTS: Outcomes management had no significant effect on total duration of mechanical ventilation or length of stay in the hospital, days of mechanical ventilation without tracheostomy, days of mechanical ventilation with tracheostomy, or outcome (weaned, withdrawal from mechanical ventilation, death, or transfer without weaning). However, duration of mechanical ventilation was 1.3 days shorter, length of stay in the hospital was 2.1 days shorter, and the cost per case was $ 3341 less for patients in the outcomes-managed group than for patients in the non-outcomes-managed group. CONCLUSION: Outcomes-managed care did not have a significant effect on duration of ventilation, length of stay in the hospital, or outcome in patients receiving long-term mechanical ventilation.

Are frequent inner cannula changes necessary?: A pilot study.

OBJECTIVE: To determine the incidence of obstruction and colonization in adult patients in the surgical and medical intensive care units who received inner cannula changes daily versus those who did not. DESIGN: Quasi-experimental prospective study using a convenience sample of patients randomly assigned to one of two methods. SETTING: Mid-Atlantic university-affiliated tertiary care center. PATIENTS: Sixty patients within 24 hours of receiving a surgical tracheostomy. OUTCOME MEASURES: Obstruction and bacterial colonization of inner cannula. INTERVENTIONS: All inner cannulas were checked daily for obstruction and cultured on postoperative days 1 and 3. RESULTS: No statistically significant difference was noted in colonization (p = 0.13) between protocols, and no obstructions were noted in either. CONCLUSION: The study suggests that the routine practice in critical care units of changing tracheostomy inner cannulas may be unnecessary. Although the results of this study are limited, and may not be generalized to other populations, it demonstrates that practice standards related to the care of tracheostomy inner cannula need to be challenged.

Detection of the extracellular proteases of Bacteroides nodosus in polyacrylamide gels: a rapid method of distinguishing virulent and benign ovine isolates.

The extracellular proteases of Bacteroides nodosus were separated electrophoretically on polyacrylamide slab gels at pH 8 . 8. Proteolytic activity was detected by placing the gel slab on a layer of gelatin-agar and allowing hydrolysis of the gelatin to occur. After two hours at 37 degrees C, the unhydrolysed gelatin was precipitated with mercuric chloride in acid. The proteolytic zymograms of 14 benign strains were identical. The zymograms of 10 virulent strains yielded two closely related sets of proteases. The reproducible difference observed between the respective zymograms readily provides a rapid diagnostic test to assist in the identification of benign and virulent strains of B nodosus.

Structural failure of a Starr-Edwards aortic track valve.

Structural failure of a Model 2400 Starr-Edwards aortic track valve occurred suddenly, 4 years after implantation. At operation, the valve cage was removed from the descending aorta. Examination of the excised prosthesis disclosed minimal cloth wear and no evidence of infective growth; however, three struts were fractured above their insertion into the valve ring. To our knowledge, this type of valve malfunction has not been previously noted.

Hexachlorobenzene contamination: its effects in a Louisiana population.

Plasma hexachlorobenzene (HCB) residues in a Louisiana population exposed through the transportation and disposal of chemical waste containing HCB averaged 3.6 plus or minus 4.3 parts per billion (ppb) in a sample of 86 people. The highest level was 345 ppb in a waste disposal facility worker while the highest level in the general population was 23 ppb. There was no evidence of cutaneous porphyria by history or skin examination. Males had significantly higher residues than females (4.71 vs. 2.79 ppb) but there were no age differences. A possible association between HCB residues and coproporphyrin and lactic dehydrogenase was found. Only 2 of 48 meals sampled were positive for HCB. There was a correlation between HCB levels in household dust and plasma levels. Perchloroethylene and carbon tetrachloride production workers had plasma HCB levels of up to 233 ppb.