Homozygosity for a HERG potassium channel mutation causes a severe form of long QT syndrome: identification of an apparent founder mutation in the Finns.

OBJECTIVES: We studied the clinical characteristics and molecular background underlying a severe phenotype of long QT syndrome (LQTS). BACKGROUND: Mutations of cardiac ion channel genes cause LQTS, manifesting as increased risk of ventricular tachycardia and sudden death. METHODS: We studied two siblings showing prolonged QT intervals corrected for heart rate (QTc), their asymptomatic parents with only marginally prolonged QTc intervals and their family members. The potassium channel gene HERG was screened for mutations by deoxyribonucleic acid sequencing, and the electrophysiologic consequences of the mutation were studied in vitro using the whole-cell patch-clamp technique. RESULTS: A novel missense mutation (L552S) in the HERG channel, present in the homozygous state in the affected siblings and in the heterozygous state in their parents, as well as in 38 additional subjects from six LQTS families, was identified. One of the homozygous siblings had 2:1 atrioventricular block immediately after birth, and died at the age of four years after experiencing unexplained hypoglycemia. The other sibling had an episode of torsade de pointes at the age of two years. The mean QTc interval differed significantly (p < 0.001) between heterozygous symptomatic mutation carriers (500 +/- 59 ms), asymptomatic mutation carriers (452 +/- 34 ms) and noncarriers (412 +/- 23 ms). When expressed in vitro, the HERG-L552S formed functional channels with increased activation and deactivation rates. CONCLUSIONS: Our data demonstrate that homozygosity for a HERG mutation can cause a severe cardiac repolarization disorder without other phenotypic abnormalities. Absence of functional HERG channels appears to be one cause for intrauterine and neonatal bradycardia and 2:1 atrioventricular block.

Advances in the management of acute respiratory distress syndrome: protective ventilation.

The approach to mechanical ventilation has been revolutionized by new insights into the pathogenesis of respiratory failure in acute respiratory distress syndrome (ARDS). Concepts such as low-volume ventilation, permissive hypercapnia, inverse ratio ventilation, best and intrinsic positive end-expiratory pressure, airway shear, pressure volume curves, inflection points, and prone positioning have radically transformed thinking about ventilator management. Since 1966, more than 8000 ARDS-related publications have appeared. Studies highlighting the experimental basis for innovations in mechanical ventilation are presented. Selected clinical series that exemplify the use of these new strategies are reviewed, to demonstrate how key experimental and clinical research has altered our understanding about what works, and why. Mismanagement of mechanical ventilation causes lung injury and increases mortality. The strategy of protective ventilation has provided the first substantial reduction of mortality in the history of ARDS.

Clinical observation of the temporal association between crack cocaine and duodenal ulcer perforation.

HYPOTHESIS: To determine if a cause-effect relationship exists between crack cocaine use and duodenal ulcer perforation (DUP). PATIENTS AND METHODS: A retrospective study was conducted of all patients undergoing emergency surgical management for peptic ulcer disease over a 6-year period at a large inner-city municipal teaching hospital. The hospital records of 78 consecutive patients presenting with complications of peptic ulcer disease between April 1990 and April 1996 were reviewed. Group A (n = 24) consisted of patients with confirmation of crack cocaine usage within 8 hours of clinical presentation; group B (n = 54) consisted of patients with no antecedent history of crack cocaine use. Demographic data, timing of drug use, clinical presentation, laboratory and radiographic findings, toxicology screening, operative findings, and postoperative course were compared between the two groups. RESULTS: Both groups revealed a similar gender distribution, tobacco use, prior peptic ulcer symptoms, and laboratory findings. Group A patients were younger (t test, P = 0.01) and more likely to present with perforation, whereas patients in group B presented with a combination of symptoms (chi square, P = 0.03). Duodenal ulcer perforation was present in 75% of patients in group A compared with 46% of patients in group B (chi square, P = 0.04). Group B patients had a significantly longer hospital stay compared with those in group A (t test, P = 0.01). Both crack cocaine and alcohol are independent predictors of duodenal ulcer perforation. CONCLUSIONS: Patients with recent use of crack cocaine and/or alcohol are more likely to present with duodenal perforations. Although a temporal association between crack cocaine use and duodenal ulcer perforation was demonstrated, this study does not confirm a cause-effect relationship. A prospective cohort study is needed to clarify the pathogenesis of this potential cause-effect relationship.

Pontine-crossed paralysis consequent to multiple trauma: case report.

The case of a multiple trauma victim with a brain-stem injury, resulting in a syndrome of pontine-crossed paralysis, is presented. Demonstration of these disorders in the setting of multiple trauma is highly unusual, but the diagnosis is established quickly and accurately through magnetic resonance imaging. A possible mechanism of injury is presented for discussion.

Emerging and reemerging microbial threats. Nosocomial fungal infections.

The incidence of nosocomial fungal infections had been increasing steadily for the past 25 years. Although they were once believed to be of little clinical consequence, there is now compelling evidence that fungal agents represent a bona fide microbial threat with substantial morbidity and high mortality. Reporting on a series of 30447 nosocomial fungal infections that occurred in the decade from 1980 to 1990, Beck-Sague and Jarvis noted increases in incidence from 90% to 175%. Infection rates rose from 2.0 per 1000 discharges to as high as 6.6 infections per 1000 discharges. Fungal infections increased at all major anatomic sites, including surgical wounds, lung, urinary tract, and bloodstream. Candida species accounted for 78.3% of nosocomial fungal infections, while torulopsis species and aspergillus species accounted for 7.3% and 1.3%, respectively.

Videothoracoscopy an effective method for evaluating and managing thoracic trauma patients.

BACKGROUND: The objective of this study was to assess the diagnostic and therapeutic effectiveness of videothoracoscopy in thoracic trauma patients. METHODS: The design was a retrospective review. The setting was a major trauma center at an urban county hospital. Forty-one hemodynamically stable patients sustaining thoracic trauma were reviewed (34 penetrating and 7 blunt injuries). In the acute setting (< 24 h), videothoracoscopy was used for continued bleeding(6) and suspected diaphragmatic injury(17). Thoracoscopy was used in delayed settings (> 24 h) for treatment of thoracic trauma complications(18) including clotted hemothorax(14), persistent air leak(1), widened mediastinum(1), and suspected diaphragmatic injury(2). RESULTS: The average Injury Severity Score (ISS) of these patients was 18.9 +/- 10.0. Three of 6 patients (50%) with continued bleeding were successfully treated thoracoscopically. Nine of 10 (90%) diaphragmatic injuries were confirmed by thoracoscopy, and 7 of these 9 patients (77%) were repaired thoracoscopically. Thirteen of 14 patients (93%) with clotted hemothoraces and one with a persistent air leak were treated successfully using thoracoscopy. An aortic injury was ruled out in one patient. CONCLUSIONS: Videothoracoscopy is a safe, accurate, minimally invasive, and potentially cost-effective method for the diagnosis and therapeutic management of thoracic trauma patients.

General surgery.

Stereotactic breast biopsy appears to be as accurate for diagnosis as open biopsy, at one-third to one-half the cost. There is increasing evidence that laparoscopy is safe and effective for determining peritoneal penetration and extent of injury in penetrating abdominal wounds.

Gasless laparoscopy and conventional instruments. The next phase of minimally invasive surgery.

OBJECTIVE: To assess the capability of a retractor system that permits laparoscopic surgery without pneumoperitoneum and to determine if the system facilitates the use of conventional surgical instruments during minimally invasive surgery. DESIGN: Prospective evaluation and data collection with review. SETTING: University-affiliated county hospital. PATIENTS: Twenty-nine male and 29 female subjects evaluated prospectively via 27 trauma-related and 31 elective procedures. METHODS: Fifty-eight laparoscopic procedures were performed between July 1992 and February 1993 with a system consisting of an intra-abdominal fan retractor and an electrically powered mechanical arm using conventional surgical and laparoscopic instruments. RESULTS: Gasless laparoscopy was used in the evaluation of 27 patients with abdominal trauma (11 gunshot wounds, 11 stab wounds, and five blunt injuries). The need for celiotomy was obviated in 20 (74%) of 27 cases. Three enterotomies, two diaphragmatic lacerations, and one gastric perforation were repaired with conventional instruments. Gasless laparoscopic techniques were also used in cholecystectomy (n = 26), diagnostic laparoscopy (n = 3), and appendectomy (n = 2). Exposure similar to that obtained by pneumoperitoneum was obtained in 30 (97%) of 31 cases. One major (trocar tip enterotomy) and two superficial wound infections occurred in this group. The ability to use conventional surgical instruments was advantageous in several cases. CONCLUSIONS: Comparable exposure was achieved in this cohort of patients with gasless laparoscopy. The use of conventional surgical instruments provides an advantage with this technique. Further improvements in abdominal wall lift systems and modification of existing surgical instruments may expand the role of gasless laparoscopy.

Surgery 2001. Twilight of the gods.

Statistics documenting the relentless rise of women in American medicine, primary care specialties, and surgery are presented. Representation of women in many surgical societies, on journal editorial boards, and in surgical texts does not appear to have kept pace. The participation of women surgeons in each of these activities ranges from 0.8% to 1.7%, equivalent to the percentage of women in general surgery before 1975. Comparison is made with women surgeons in an open national society (8.2%), an open regional society (6.9%), an open editorial board (7.5%), and a recently published textbook of surgery (8.2%). These proportions parallel the current 6.3% of women in general surgery and support the premise that women are at least as likely as their male colleagues to participate in the professional activities of the surgical establishment. During the waning years of the 20th century, ever-increasing numbers of qualified women will come forward to join the hierarchy of American surgery.

Accuracy of computed tomography in predicting adrenal tumor size.

We undertook a multi-institutional, retrospective study of 51 patients with adrenal tumors (pheochromocytomas, functioning and nonfunctioning cortical adenomas, cysts and carcinomas). All patients had computed tomography (CT) with a maximum of 5 millimeter cuts the week before undergoing complete adrenalectomy. Pathologists were asked to measure the tumor to the nearest 0.1 centimeter. Tumor size obtained from pathologic reports (actual size) and CT reports (estimated size) were compared. Adrenal tumors were divided into two groups on the basis of size--tumors with actual size of 6 centimeters or greater and tumors with actual size of less than 6 centimeters. Statistical analysis was performed with Newman-Keuls analysis of variance. After controlling for tumor type and for the institution at which the measurement was made, we found that CT consistently underestimated adrenal tumor size in both tumor groups. Moreover, the average, underestimated difference for tumors 6 centimeters or greater was 32 percent, but 47 percent for tumors less than 6 centimeters (p = 0.060). CT seemed to underestimate the size of small adrenal tumors more than large tumors. Because the decision to operate on solid, nonfunctioning adrenal tumors is based on tumor size and because CT is currently the standard technique used to estimate size, our findings need to be considered before undertaking surgical treatment.

Enhancement of urine output and glomerular filtration in acutely oliguric patients using low-dose norepinephrine.

A prospective clinical trial was initiated to test the hypothesis that low-dose norepinephrine enhances urine output and renal function in oliguric surgical patients. Norepinephrine (0.05 or 0.1 micrograms/kg/min) was infused into nine oliguric (< or = 0.5 ml/kg/hr), volume-replete, hemodynamically stable patients. There was an average increase of urine output of 13 ml/hr (48% over baseline) and an increase of 31.7 ml/min (47% over baseline) in creatinine clearance. Both these results were statistically significant. Mean arterial pressure was the only hemodynamic parameter that changed significantly, rising an average of 12 mm Hg. We conclude that low-dose norepinephrine infusion may enhance renal function and urine output in acutely oliguric surgical patients who have been appropriately fluid resuscitated.

Impact of programmed reading on ABSITE performance. American Board of Surgery In-Training Examination.

To test the hypothesis that a program of regular reading and discussion would result in significant improvement in the surgical database as measured by the American Board of Surgery In-Training Examination (ABSITE), we conducted a 2-year prospective study. The study group, which was comprised of 40 residents, was compared with a control group of 44 residents enrolled in the residency during the 2 years that preceded the study period. Neither reading effort nor discussion group attendance correlated strongly with ABSITE performance among first-year residents. At this level, ABSITE scores correlated best with National Board of Medical Examiners Part I scores (r = 0.699, p = 0.002). In contrast, second-year through fifth-year residents showed a cumulative improvement across the residency (80 versus 180 standard score points, p = 0.048). Individual resident improvement correlated highly with reading effort (r = 0.79, p less than 0.001). There was little measurable effect from attending discussion sessions. We conclude that the surgical database can be improved by a program of regular reading and that the magnitude of the improvement is directly proportional to the reading effort.