Improved Antiviral Activity of a Polyamide Against High-Risk Human Papillomavirus Via N-Terminal Guanidinium Substitution.

We report the synthesis of two novel pyrrole-imidazole polyamides with N-terminal guanidinium or tetramethylguanidinium groups and evaluate their antiviral activity against three cancer-causing human papillomavirus strains. Introduction of guanidinium improves antiviral activity when compared to an unsubstituted analog, especially in IC90 values. These substitutions change DNA-binding preferences, while binding affinity remains unchanged.

Preoperative spirometry before abdominal operations. A critical appraisal of its predictive value.

Preoperative spirometry is commonly ordered before abdominal surgery, with the goal of predicting and preventing postoperative pulmonary complications. We assessed the evidence for this practice with a systematic literature search and critical appraisal of published studies. The search identified 135 clinical articles, of which 22 (16%) were actual investigations of the use and predictive value of preoperative spirometry. All 22 studies had important methodological flaws that preclude valid conclusions about the value of screening preoperative spirometry. The available evidence indicates that spirometry's predictive value is unproved. Unanswered questions involve (1) the yield of spirometry, in addition to history and physical examination, in patients with clinically apparent lung disease; (2) spirometry's yield in detecting surgically important occult disease; and (3) its utility, or beneficial effect on patient outcome. Spirometry's full potential for risk assessment in the individual patient has not yet been realized.

An efficient chiral moderator prepared from inexpensive (+)-3-carene: synthesis of the HIV-1 non-nucleoside reverse transcriptase inhibitor DPC 963.

The beta-amino alcohol 4 beta-morpholinocaran-3 alpha-ol is prepared by addition of morpholine to alpha-3,4-epoxycarane utilizing anhydrous magnesium bromide as Lewis acid promoter. The enantiopure amino alcohol is uniquely effective as a chiral moderator for the addition of lithium cyclopropylacetylide to an unprotected N-acylketimine. This reaction provides an efficient route to the second generation NNRTI drug candidate DPC 963.

Physiologic management of diabetic ketoacidemia. A 5-year prospective pediatric experience in 231 episodes.

OBJECTIVE: To determine whether gradual rehydration in moderate and severe diabetic ketoacidemia (DKA) can safely prevent untoward declines in calculated effective osmolality (Eosm) early in treatment and, hence, help prevent major central nervous system complications. DESIGN: Prospective study. SETTING: Three tertiary care hospitals. PATIENTS: Two hundred thirty-one consecutive episodes of DKA in 149 patients aged 10 months to 20 years admitted during a 5-year period. INTERVENTIONS: Insulin therapy in addition to rehydration using an estimated volume of deficit with planned administration over 48 hours; initial administration of rehydration solutions with an osmolality approximating that of the patient; and intensive patient monitoring. MEASUREMENTS: Mean lowest calculated Eosm (EosmL) during the first 24 hours of treatment; trend of the concentration of sodium in serum in the first 12 hours of treatment; comparison of pretreatment serum concentrations of glucose, urea nitrogen, and corrected sodium between mildly and very severely dehydrated patients; and patient outcome. RESULTS: A mean (+/- SD) EosmL of 285.8 +/- 10.5 mOsm/kg Nater and an increase in the concentration of sodium in serum in 90% of episodes were documented. There were statistically significant differences in serum concentrations of glucose, urea nitrogen, and corrected sodium in mildly vs very severely dehydrated patients. There were no deaths or near-death episodes. CONCLUSIONS: Management of moderate and severe DKA with a 48-hour planned rehydration is safe and prevents untoward declines in Eosm. Coupled with intensive monitoring, gradual rehydration can protect against life-threatening increases in intracranial pressure and brain herniation.

Aspiration pneumonia, anaerobic infections, and lung abscess.

Anaerobic pleuropulmonary infections are common in the setting of aspiration. Treatment is with penicillin or in mixed infections, penicillin and other appropriate antimicrobial agents. Four syndromes are commonly recognized. Simple pneumonitis resolves promptly with antibiotic therapy. If treatment is delayed, simple pneumonitis may evolve into a more fulminant process of necrotizing pneumonia with a significant mortality despite antibiotic therapy. Lung abscess, typically a subacute or chronic infection, responds well to antibiotic therapy so long as the cavity is drained via the communicating bronchus. Empyema requires surgical drainage by either closed or open thoracostomy if resolution is to be achieved.

The effect of an ambulatory internal medicine rotation on students' career choices.

PURPOSE: To assess the effect of an ambulatory care experience on medical students' perceptions of internal medicine and their choices of careers (as measured by residency selections). METHOD: In 1990-91, the 196 third-year students enrolled in the 12-week internal medicine clerkship at the University of Texas Medical School at San Antonio were randomized to a curriculum that included a three-week ambulatory care component or to a traditional, exclusively inpatient curriculum. The ambulatory curriculum included the evaluation of walk-in-patients, exposure to community internists, and a lecture series. The students' perceptions of internal medicine were surveyed before and after the clerkship. Their career choices were determined by their residency selections at graduation. Data analysis employed chi-square tests, t-tests, and logistic regression. RESULTS: Of the 196 students, 184 (76 in the ambulatory and 108 in the traditional curricula) provided complete data. The ambulatory care students were somewhat more likely to enter an internal medicine residency (odds ratio = 1.49; 95% CI, 0.72 to 3.09) than were the traditional students. The ambulatory care students' perceptions of internal medicine did not change significantly from before to after the clerkship. CONCLUSION: The ambulatory curriculum had a modest but favorable effect on the students' selections of careers in internal medicine, but was not associated with changes in their perceptions of internal medicine.

A comparison of two methods for facilitating clinical data integration by medical students.

Two important charting strategies to help students organize patients' data are Weed's problem-oriented medical record (POMR) and Russell's condition diagram (CD). The authors conducted the present study in 1987 to determine whether either was superior for clinical data integration. Sophomore medical students at The University of Texas Medical School at San Antonio indicated whether they preferred the POMR, the CD, or neither. They were then divided into three study groups according to their preferences, with the POMR and CD groups receiving 80 hours of training and the control group receiving only the standard preclinical training. Each student then examined a standardized patient and wrote an open-ended report about the patient's medical problem. After examining a second patient, students were asked to write a structured report providing information about each of ten components of diagnosis. Both the CD and the POMR groups scored numerically higher on the structured type of report than did the controls, but only the CD group scored significantly higher. The CD group also scored higher than did the POMR group on both types of report, but the differences were not statistically significant. This study indicates that the clinical reasoning of medical students can be enhanced by focused training in either the CD or the POMR methods. It suggests that the CD format may be particularly helpful for students with lower academic achievement.

Maintaining normal intracranial pressure in a rabbit model during treatment of severe diabetic ketoacidemia.

Increased intracranial pressure (ICP) resulting in death or neurologic morbidity continues to complicate traditional management of diabetic ketoacidemia (DKA) in pediatric patients. When ICP or cerebrospinal fluid pressures have been measured, correction of hyperglycemia in animals and treatment of DKA in humans have consistently resulted in pathologic increases in ICP. We hypothesized that elevations in ICP can be minimized if changes in effective osmolality (Eosm) are controlled during treatment of DKA. During a six-hour study period, three groups of rabbits were studied: a normal control group of nondiabetic animals (Cnor, n = 10), a control group of animals with DKA (CDKA, n = 8), and an experimental group of animals with DKA (EDKA, n = 8). There was no significant difference between the two groups with DKA regarding pretreatment degree of dehydration, blood pressure, hyperglycemia, acidemia or ICP. During the treatment period, Cnor received maintenance fluids only. CDKA received insulin and an assumed volume of deficit (150 ml/kg) along with maintenance fluids and urinary output replacement with 0.45% NaCl. EDKA received insulin and one-half the volume of deficit calculated by the weight lost with 0.9% NaCl plus maintenance fluids. There was no significant difference between CDKA and EDKA regarding the rate at which DKA was corrected. While CDKA demonstrated a progressive and statistically significant increase in ICP, EDKA exhibited no such increase in ICP compared to normal, nondiabetic controls (Cnor) during treatment. Changes in Eosm during treatment in CDKA compared to Cnor and in CDKA compared to EDKA were significantly greater (p < .01), however, changes in EOSM in EDKA compared to Cnor were not significant. These data support the clinical observation that decreasing EOSM during treatment of DKA is associated with increased ICP and suggest that DKA can be treated effectively with i.v. fluids and insulin without increasing ICP.

Brain osmoregulation during extreme and moderate dehydration in a rat model of severe DKA.

To determine if osmoprotective molecules accumulate in the brain during severe DKA with extreme (DKA-E) and moderate (DKA-M) dehydration, Fischer 344 rats (250-350g) were given STZ 45 mg/kg (i.p.) and allowed food and water ad lib. DKA-M received NaCl 77 mmol/L 60 ml/kg (i.p.) q 4 hrs. on day 2. All rats were anesthetized and sacrificed at 48 hrs. Half of each brain was used to measure water content (BWC) and half to measure Na+, K+, and organic osmoles by HPLC. Just prior to expiration, values for mean concentration of serum glucose (mmol/L) percent weight loss and median blood pH for DKA-E were 33.4, 19%, 6.98; for DKA-M, 16.8, 7.5% and 6.84, respectively. Means +/- SEM were compared by Student's t-test. Percent BWC was 76.3, 77.3 and 77.6 in DKA-E, DKA-M and normal controls, respectively (NS). Brain Na+ and K+ were increased in DKA-M compared to controls (p < .05) but not significantly different in DKA-E compared to controls. Of organic osmoles measured (umol/g wet weight) taurine was significantly increased (p < .01) in DKA-E and DKA-M (8.04 +/- .39 and 9.73 +/- .78, respectively) as compared to controls (5.92 +/- .35) as was myoinositol in DKA-E compared to controls (9.96 +/- .39 vs. 8.87 +/- .28) (p < .05) and urea in DKA-E as compared to controls (14.24 +/- 3.9 vs. 4.14 +/- .52) (p < .01). DKA-M were not significantly different for brain myoinositol or urea as compared to control animals. There was no significant difference in brain glutamine between either study group and controls. Preservation of brain water despite systemic dehydration can be partly explained by increased brain concentrations of osmoprotective molecules. Such adaption in the clinical setting of DKA warrants a cautious repair of dehydration and hyperosmolality.

Colostomy and colostomy closure.

A series of 181 adult patients subjected to colostomy was studied, almost all of whom had disease rather than injury. The complication rate was 28 per cent. One hundred of these patients had a subsequent colostomy closure with a complication rate of 17 per cent. Of the patients who had both procedures, 35 (35 per cent) had one or more significant complications. The causes and prevention of these complications are described.

Experience with the Tajima procedure in primary and secondary repair in unilateral cleft lip nasal deformity.

The method of cleft lip nasal deformity repair described by Tajima and Maruyama appears to produce superior results compared to other methods we had tried. A modified technique of suture placement, aided by our special nasal retractor, greatly simplifies suture placement. In both primary and secondary cases, significant and maintained improvement has been achieved with what is a comparatively simple and standardized procedure.

The dorsal thoracic fascia: anatomic significance with clinical applications in reconstructive microsurgery.

The anatomic distribution and potential arterial flow patterns of the circumflex scapular artery were investigated by Microfil injection. These studies demonstrated that the circumflex scapular artery lies within the dorsal thoracic fascia, which plays a significant role in the circulation of the overlying skin and subcutaneous tissue. We conclude that scapular/parascapular flaps are fasciocutaneous flaps, the dorsal thoracic fascia can be transferred as a free flap without its overlying skin and subcutaneous tissue, and intercommunication exists between the myocutaneous perforators of the latissimus dorsi myocutaneous flap and the vascular plexus of the dorsal thoracic fascia. We present microvascular cases in which the vascular properties of the dorsal thoracic fascia facilitated wound closure with free fascia flaps or expanded cutaneous or myocutaneous flaps.

The LPD-II: a modified locked percutaneous device that permits safe subcutaneous access.

A locked percutaneous device, the LPD-I (previously described as LPD), is effective in overcoming the problems of skin downgrowth and local tissue infection; however, it can only be implanted at a site providing adequate subcutaneous adipose tissue to attach to the subcutaneous connector of the LPD-I. A modified device, the LPD-II, has been developed that has a thin dome and skin connector but does not have a subcutaneous tissue connector. In addition, a newly designed structure called the skin stop collar (SSC) has been developed. It is positioned just beneath the mesh collar described in the LPD-I to further improve the function of the LPD-II. Six rabbits were implanted with one LPD-II without the SSC (group 1) and five rabbits were implanted with one LPD-II with the SSC (group 2). For more than 6 months, two of the implants in group 1 rabbits were successful. Four of the implants in group 2 rabbits were successful for more than 1 year. One of the animals in group 2 died of causes unrelated to the device. We conclude the following: the mesh collar skin connector can function well as a locked percutaneous device without the subcutaneous tissue connector; the LPD-II can be implanted in any site and does not require the presence of subcutaneous adipose tissue; and the SSC may increase the success rate of LPD-II implantation provided the mesh collar is made of soft material.

A novel percutaneous barrier device that permits safe subcutaneous access.

Successful subcutaneous access is important for optimal management of internal artificial organs and treatment of many diseases. However, skin downgrowth and tissue infection are still significant problems in the use of devices that require long-term subcutaneous access. The authors developed a new percutaneous device that provides a unique biologic boundary with surrounding connective tissue while minimizing the risk of complications. This new percutaneous device is made of a circumferential, strong, thin, and flexible mesh collar with millimeter size holes for connecting the structure. It has two distinct functional portions: a connecting zone and a sealing line. The most important features of the structure are: 1) Connective tissue grows through the millimeter size pores of the connecting zone to form a strong bond between the device and healthy tissue. 2) The millimeter size pores of the connecting zone allow capillaries to grow through its entire surface, ensuring sufficient blood supply. 3) The tissue of the connecting zone and the device surface form a biosealed junction (sealing line). This sealing line is protected by the connecting zone and is free from external forces acting on local skin. 4) The device is generally functional immediately after surgical implantation. The subcutaneous perimeter of the functional dome contains extruded rigid rings of millimeter size holes permitting growth of subcutaneous tissue through the device. This functions as the minor connecting structure of the device. Four of five implanted rabbits have remained healthy 8 months postimplantation without antibiotic administration. The fifth rabbit died 4 months postimplantation for reasons unrelated to the device. Gross or histopathologic inspection revealed no signs of tissue injury or inflammation. Growth of healthy connective tissue was clearly observed. These results indicate this percutaneous device can provide a strong, stable, and effective connection to internal organs without bioboundary damage, skin downgrowth, or tissue infection.

Heart disease in children.

Advances in the understanding of the pathophysiology, diagnosis, and medical and surgical management of neonates with cardiovascular disease has led to their improved survival rates. These improvements have resulted in an increased number of pediatric patients presenting to the primary care physician's office with underlying heart disease. Understanding the genetic, congenital, or acquired etiologies to the various pediatric heart diseases is crucial to preventing these lesions and treating these patients.

Compiling the identifying features of bacterial endocarditis. Vague clues may point to this dangerous infection.

Bacterial endocarditis is a life-threatening disease. Before the advent of antibiotics, its mortality rate was nearly 100%, but with today's diagnostic and therapeutic advances, it can be successfully managed in most cases. In this article, Drs Harris and Steimle explain the changes that occur when someone, who usually has an underlying cardiac defect, contracts bacteremia with an organism likely to adhere to heart valve surfaces. They describe risk factors, clinical presentations, identification of causative organisms, and empirical and specific therapy. A case report illustrates the many possible manifestations of the disease.