The Shiga Toxin Receptor Globotriaosylceramide as Therapeutic Target in Shiga Toxin E. coli Mediated HUS.

In 90% of the cases, childhood hemolytic uremic syndrome (HUS) is caused by an infection with the Shiga toxin (Stx) producing E. coli bacteria (STEC-HUS). Stx preferentially binds to its receptor, the glycosphingolipid, globotriaosylceramide (Gb3), present on the surface of human kidney cells and various organs. In this study, the glycosphingolipid pathway in endothelial cells was explored as therapeutic target for STEC-HUS. Primary human glomerular microvascular endothelial cells (HGMVECs) and human blood outgrowth endothelial cells (BOECs) in quiescent and activated state were pre-incubated with Eliglustat (Cerdelga®; glucosylceramide synthase inhibitor) or Agalsidase alpha (Replagal®; human cell derived alpha-galactosidase) in combination with various concentrations of Stx2a. Preincubation of endothelial cells with Agalsidase resulted in an increase of α-galactosidase activity in the cell, but had no effect on the binding of Stx to the cell surface when compared to control cells. However, the incubation of both types of endothelial cells incubated with or without the pro-inflammatory cytokine TNFα in combination with Eliglustat resulted in significant decrease of Stx binding to the cell surface, a decrease in protein synthesis by Stx2a, and diminished cellular Gb3 levels as compared to control cells. In conclusion, inhibition of the synthesis of Gb3 may be a potential future therapeutic target to protect against (further) endothelial damage caused by Stx.

Cell Biological Responses after Shiga Toxin-1 Exposure to Primary Human Glomerular Microvascular Endothelial Cells from Pediatric and Adult Origin.

Hemolytic uremic syndrome (HUS) is characterized by a triad of symptoms consisting of hemolytic anemia, thrombocytopenia and acute renal failure. The most common form of HUS is caused by an infection with Shiga toxin (Stx) producing Escherichia coli bacteria (STEC-HUS), and the kidneys are the major organs affected. The development of HUS after an infection with Stx occurs most frequently in children under the age of 5 years. However, the cause for the higher incidence of STEC-HUS in children compared to adults is still not well understood. Human glomerular microvascular endothelial cells (HGMVECs) isolated and cultured from pediatric and adult kidney tissue were investigated with respect to Stx binding and different cellular responses. Shiga toxin-1 (Stx-1) inhibited protein synthesis in both pediatric and adult HGMVECs in a dose-dependent manner at basal conditions. The preincubation of pediatric and adult HGMVECs for 24 hrs with TNFα resulted in increased Stx binding to the cell surface and a 20-40% increase in protein synthesis inhibition in both age groups. A decreased proliferation of cells was found when a bromodeoxyuridine (BrdU) assay was performed. A trend towards a delay in endothelial wound closure was visible when pediatric and adult HGMVECs were incubated with Stx-1. Although minor differences between pediatric HGMVECs and adult HGMVECs were found in the assays applied in this study, no significant differences were observed. In conclusion, we have demonstrated that in vitro primary HGMVECs isolated from pediatric and adult kidneys do not significantly differ in their cell biological responses to Stx-1.

Primary Human Derived Blood Outgrowth Endothelial Cells: An Appropriate In Vitro Model to Study Shiga Toxin Mediated Damage of Endothelial Cells.

Hemolytic uremic syndrome (HUS) is a rare disease primarily characterized by hemolytic anemia, thrombocytopenia, and acute renal failure. Endothelial damage is the hallmark of the pathogenesis of HUS with an infection with the Shiga toxin (Stx) producing Escherichia coli (STEC-HUS) as the main underlying cause in childhood. In this study, blood outgrowth endothelial cells (BOECs) were isolated from healthy donors serving as controls and patients recovered from STEC-HUS. We hypothesized that Stx is more cytotoxic for STEC-HUS BOECs compared to healthy donor control BOECs explained via a higher amount of Stx bound to the cell surface. Binding of Shiga toxin-2a (Stx2a) was investigated and the effect on cytotoxicity, protein synthesis, wound healing, and cell proliferation was studied in static conditions. Results show that BOECs are highly susceptible for Stx2a. Stx2a is able to bind to the cell surface of BOECs with cytotoxicity in a dose-dependent manner as a result. Pre-treatment with tumor necrosis factor alpha (TNF-α) results in enhanced Stx binding with 20-30% increased lactate dehydrogenase (LDH) release. Endothelial wound healing is delayed in a Stx2a-rich environment; however, this is not caused by an effect on the proliferation rate of BOECs. No significant differences were found between control BOECs and BOECs from recovered STEC-HUS patients in terms of Stx2a binding and inhibition of protein synthesis.

The genetics of atypical hemolytic uremic syndrome.

Atypical hemolytic uremic syndrome (aHUS) is a disorder characterized by thrombocytopenia and microangiopathic hemolytic anemia due to endothelial injury. aHUS is felt to be caused by defective complement regulation due to underlying genetic mutations in complement regulators or activators, most often of the alternative pathway. Mutations causing aHUS can be subdivided into two groups, loss of function mutations (affecting factor H, factor H-related proteins, membrane co-factor protein, and factor I), and gain of function mutations (affecting factor B and C3). As more information becomes available on the relationship between specific mutations and clinical outcome, complete genetic workup of aHUS patients becomes more and more important. In this review, we will discuss the genetic background of aHUS, the role of complement for aHUS pathogenesis, and the different groups of specific mutations known to be involved in the pathogenesis of aHUS.

Antiemetic efficacy of prophylactic dimenhydrinate (Dramamine) vs ondansetron (Zofran): a randomized, prospective trial inpatients undergoing laparoscopic cholecystectomy.

BACKGROUND: The prophylactic administration of dimenhydrinate (Dramamine) is as effective as the use of ondansetron (Zofran) in preventing postoperative nausea and vomiting (PONV) in patients undergoing elective laparoscopic cholecystectomy. A prospective double-blind randomized study was performed in a tertiary care referral center. METHODS: For this study, 128 American Society of Anesthesiology (ASA) physical statuses I, II, and III patients were randomly assigned to receive either ondansetron 4 mg intravenously (IV) at $17 per dose (group 1) or dimenhydrinate 50 mg IV at $2.50 per dose (group 2) before induction of anesthesia. The end points evaluated were frequency of PONV, need for rescue antiemetics, need for overnight hospitalization secondary to persistent nausea and vomiting, and frequency PONV 24 h after discharge. RESULTS: Chi-square tests and student's t-test were used to determine the significance of differences among groups. Of the 128 patients enrolled in this study, 20 were excluded: 15 patients received an additional antiemetic preoperative; 4 were converted to open cholecystectomies; and 1 procedure was aborted due to carcinomatosis. Of the 108 remaining participants, 50 received ondansetron (group 1) and 58 received dimenhydrinate (group 2). Both groups were well matched for demographics including gender, ASA class, and history of motion sickness. The need for rescue antiemetics occurred in 34% of group 1 and 29% of Group 2 (p = 0.376), postoperative vomiting in 6% of group 1 and 12% of group 2 (p = 0.228), and postoperative nausea in 42% of group 1 and 34% of group 2 (p = 0.422). One group 1 patient and two group 2 patients required overnight hospitalization for persistent nausea, a difference that was not significant. Rates of PONV 24 h after discharge were similar between groups 1 and 2 (10% vs 14%, p = 0.397 and 2% vs 5%, p = 0.375, respectively). CONCLUSIONS: Prophylactic administration of dimenhydrinate is as effective as the use of ondansetron in preventing PONV in patients undergoing elective laparoscopic cholecystectomy. Dimenhydrinate is the preferred drug because it is less expensive. With more than 500, 000 laparoscopic cholecystectomies performed in the United States each year, the potential drug cost savings from the prophylactic administration of dimenhydrinate instead of ondansetron exceed $7.25 million per year.

Nonoperative management of blunt liver trauma: the value of follow-up abdominal computed tomography scans.

Our hypothesis was that follow-up abdominal CT scans are not routinely necessary in patients with blunt liver injury treated nonoperatively. We conducted an 8-year retrospective review of hospital chart and outpatient clinic records. We reviewed all admission and follow-up CT scans. There were 42 adults and 12 children. There were 1 (2%) grade I, 15 (28%) grade II, 28 (52%) grade III, 8 (15%) grade IV, and 2 (4%) grade V liver injuries. Two patients died during the first 24 hours, both from associated injuries. Nonoperative management was successful in 51 (98%) of the remaining 52 patients. No follow-up abdominal CT scans were performed on 21 (40%) patients; none developed hepatic complications. An initial follow-up CT scan was obtained in 31 (60%) patients. Information from these scans directly affected management in 3 (9%) patients; in each case, the scans were prompted by a change in clinical status. One significant biloma with bile leak was managed by nasobiliary stenting and percutaneous drainage. One hepatic artery-to-portal vein fistula was obliterated by transarterial embolization. A single missed diaphragm rupture necessitated laparotomy. Additional late follow-up CT scans were obtained in 13 patients; no clinically useful information was evident on any of these examinations. We conclude that follow-up abdominal CT scans are not routinely necessary in patients with liver injuries treated nonoperatively. Selective criteria based on the severity of liver injury, presence of associated intra-abdominal pathology, and clinical parameters should dictate the need for follow-up imaging studies.

Efficient evaluation of thyroid nodules by primary care providers and thyroid specialists.

OBJECTIVE: To determine whether primary care providers and thyroid specialists at Gundersen Lutheran Medical Center are evaluating thyroid nodules efficiently by following recently published clinical guidelines. STUDY DESIGN: One-year retrospective chart review. PATIENTS AND METHODS: We reviewed patient records from 1996 and tabulated the use of fine-needle aspiration cytology, radionuclide scanning, and thyroid ultrasonography by 49 primary care physicians evaluating 81 thyroid nodules and by 5 thyroid specialists evaluating 29 thyroid nodules. The results were compared with our previous findings and those recently reported by others. RESULTS: Fine-needle aspiration cytology was widely used by both groups of Gundersen Lutheran healthcare providers. Primary care physicians used imaging studies modestly and generated $106 per patient in unnecessary costs. Thyroid specialists occasionally used radionuclide scanning but did not use thyroid ultrasonography; they generated $41 per patient in unnecessary costs. Overall, the introduction of fine-needle aspiration cytology at our institution has reduced the use of radionuclide scanning from 90% to 12% and the use of thyroid ultrasonography from 30% to 10%. We also found that the frequency of surgery in patients with thyroid nodules fell substantially, yet detection of thyroid cancer in the operative specimens increased from 16% to 43% while the cost of removing a thyroid carcinoma decreased from $64,000 to $25,000. CONCLUSIONS: Fine-needle aspiration cytology, adopted as the initial test for diagnosing thyroid nodules by most of our healthcare providers, has reduced the use of imaging studies far below the frequency reported by others and has substantially decreased the cost of thyroid nodule management.

Detection of restricted specificity of endonucleases by non-poisson analysis of their enzymatic digestion products.

Endonucleases, enzymes of the hydrolase class that cleave DNA or RNA within the substrate molecule, play numerous critical roles in molecular biologic, pharmacologic, and pathologic events as well as constitute invaluable tools used in genetic analysis, gene cloning and DNA sequencing. These enzymes have two critical parameters, activity and site specificity. The former is easily measured in commonly used assays, but the latter must be analyzed by more complex, indirect assays that are often not even carried out. We now show how both parameters can be measured directly and simultaneously in the same assay, which is not significantly more labor intensive than the commonly used activity assay. The effectiveness and accuracy of this assay was tested on a series of five bacterial restriction enzymes which recognized, respectively, 1, 2, 3, 4, and a large number (26) of reactive sites on a small, uniform DNA substrate molecule. We found that the distributions of the reaction products of all five enzymes precisely followed that predicted by the Binominal and Poisson distributions for the number of sites recognized by each enzyme, and that these distributions could be used to determine this number experimentally. In this way a measure of site specificity can be made for each enzyme as well as its activity. This new assay should be used routinely in a number of laboratories that now employ conventional assays for endonuclease activity.

Pediatric trauma management in a rural Wisconsin trauma center.

OBJECTIVE: To determine the results of pediatric trauma care managed with a cooperative effort by general surgeons and pediatric intensivists in comparison to national standards. DESIGN: Retrospective chart review. SETTING: Referral level II trauma center in rural Wisconsin. PATIENTS: All pediatric trauma patients age 16 and younger admitted to the hospital from 1990 to 1993. METHODS: Demographics, mechanisms of injury, revised trauma score (RTS), injury severity score (ISS), surgical procedures, need for intensive care, and outcome were examined. All patients were primarily managed by the trauma surgery service. Those patients requiring intensive care were managed jointly by the trauma surgery service and pediatric intensivists. Outcome was predicted by TRISS analysis; patients identified as "unexpected deaths" underwent critical clinical review to determine potential for survival. RESULTS: There were 531 pediatric trauma admissions. The mean age was 9.0 +/- 6.2 (SEM) years and two thirds of the patients were boys. Over half of all injuries were from falls, recreational activities, and motor vehicle crashes. There were few penetrating injuries. The mean RTS was 7.58 +/- 0.05, and the majority of patients had an ISS below 10. Sixty-two percent of patients required surgical procedures, most of which were orthopedic. Fourteen percent of patients were admitted to the pediatric intensive care unit. There were 13 deaths for a mortality rate of 2.4%. TRISS analysis identified six deaths as unexpected. Four drownings were not included in TRISS analysis, and there were no unexpected survivors. Of the six unexpected deaths, there were no significant management errors identified on careful review. CONCLUSIONS: Cooperation between general surgeons and pediatric intensivists can result in excellent pediatric trauma care in a rural level II trauma center.

Histological correlation of microcalcifications in breast biopsy specimens.

HYPOTHESIS: Nonpalpable malignant-appearing microcalcifications discovered by mammography geographically target the location of the most important abnormality within the breast. Core needle or open biopsy of these microcalcifications will sample or remove underlying proliferative or invasive disease. DESIGN: A prospective database of 403 consecutive patients undergoing breast biopsy for nonpalpable abnormalities from July 1, 1994, to December 31, 1996, was reviewed to identify biopsies done for indeterminate microcalcifications. Specimens showing atypical hyperplasia, carcinoma in situ, or invasive carcinoma were identified and reviewed by 1 pathologist. The position of microcalcifications larger than 100 microm were recorded in reference to the histological findings. SETTING: A 450-bed referral community teaching hospital in rural Wisconsin. PATIENTS: Indeterminant microcalcifications were identified on mammograms in 167 (41.4%) of 403 patients. Sixty-one (36.5%) of 167 biopsy specimens contained atypical hyperplasia, carcinoma in situ, or invasive carcinoma, and the slides of these 61 initial breast biopsy specimens were reviewed. MAIN OUTCOME MEASURES: Relationship of breast histopathological findings to microcalcifications. RESULTS: In these 61 specimens, 82 areas of atypical hyperplasia, carcinoma in situ, or invasive carcinoma were noted. The microcalcifications correlated with these areas in 43 (52%) of 82 areas on slide review and were present in the most important abnormality in 33 (54%) of 61 biopsy specimens. CONCLUSIONS: Indeterminant microcalcifications identified by mammography may not target the exact location of underlying breast disease. Careful evaluation of the entire biopsy specimen and close follow-up of patients with benign pathologic findings are recommended.

Effective use of percutaneous cholecystostomy in high-risk surgical patients: techniques, tube management, and results.

HYPOTHESIS: Percutaneous cholecystostomy (PC) is an effective, safe treatment in patients with suspected acute cholecystitis and severe concomitant comorbidity. DESIGN: Retrospective medical record review from March 1989 to March 1998. SETTING: Referral community teaching hospital (450 beds) in rural Wisconsin. PATIENTS: Twenty-two consecutive patients underwent PC tube placement over a 10-year period. Twenty procedures were for acute cholecystitis (14 calculous, 6 acalculous) and 2 were for diagnostic dilemmas. Nineteen (86%) of 22 patients were American Society of Anesthesiologists class 4; 3 (14%) were class 3. INTERVENTIONS: Pigtail catheters (8F-10F) placed by means of ultrasound or computed tomographic localization, with or without fluoroscopic adjunct. MAIN OUTCOME MEASURES: Thirty-day mortality, complications, clinical improvement as determined by fever and pain resolution, normalization of leukocytosis, further biliary procedures required, and outcome after drain removal. RESULTS: Twenty-two patients underwent PC for presumed acute cholecystitis based on ultrasound and clinical findings. All patients received antibiotics prior to PC for 24 or more hours. Thirty-day mortality was 36% (8 patients), reflecting severity of concomitant disease. Minor complications occurred in 3 of 22 patients. Clinical improvement occurred in 18 (82%) of 22 patients-15 (68%) within 48 hours. Follow-up of fourteen 30-day survivors is as follows: 7 (50%) had drains removed because the gallbladder was stone free, 4 (29%) had drains remaining due to persistent stones, 2 (14%) underwent cholecystectomy, and 1 (7%) awaits scheduled surgery. Only 1 (12.5%) of 8 patients developed biliary complications after drain removal, requiring endoscopic retrograde cholangiopancreatography 9 months after drain removal. One patient required urgent cholecystectomy after failure to respond to PC. This patient died of a perioperative myocardial infarction. CONCLUSIONS: Percutaneous cholecystostomy is an effective, safe treatment in patients with suspected acute cholecystitis and severe concomitant comorbidity. Laparoscopic cholecystectomy is recommended as definitive treatment for patients whose risk for general anesthesia improves in follow-up. Drains can be safely removed once all gallstones are cleared. In patients with severe concomitant disease, drains can be left with a low incidence of complications if stones remain.

The rapid low-dose (1 microgram) cosyntropin test in the immediate postoperative period: results in elderly subjects after major abdominal surgery.

BACKGROUND: Recently the rapid low-dose (1 microgram) cosyntropin test has been found to be superior to the standard (250 micrograms) rapid cosyntropin test for evaluating the hypothalamic-pituitary-adrenal axis. Because the 1-microgram test has not been studied in postoperative patients, we evaluated the test after major abdominal surgery. METHODS: We performed rapid 1-microgram cosyntropin tests in 20 patients aged 65 years or older immediately and 24 hours after uncomplicated elective abdominal surgery (group A) and in 10 patients who were suspected of having adrenal insufficiency after abdominal surgery (group B). Subsequently, 250 micrograms of cosyntropin was infused over 8 hours on 2 successive days in group B patients. RESULTS: Ninety-five percent of group A patients had normal rapid 1-microgram cosyntropin test results immediately after surgery and 90% had normal test results 24 hours postoperatively. Six group B patients had abnormal rapid 1-microgram cosyntropin test results. Additional testing indicated primary adrenal insufficiency in 2 patients and central adrenal insufficiency in 1 patient; another patient probably had primary adrenal insufficiency and 2 patients appeared to be euadrenal. Four group B patients had normal rapid 1-microgram cosyntropin test results. After additional testing, 3 of these patients appeared to have normal adrenal function; 1 probably had primary adrenal insufficiency. CONCLUSION: The rapid 1-microgram cosyntropin test accurately evaluated adrenal gland function in selected patients after uncomplicated surgery. The test, however, was difficult to interpret in unselected seriously ill postoperative patients. Therefore we recommend that postoperative patients with unexplained hypotension or other features suggestive of adrenal insufficiency who have random plasma cortisol levels less than 20 micrograms/dL be treated with glucocorticoids and the hypothalamic-pituitary-adrenal axis be studied by standard tests after recovery.

Shotgun wound management: a comparison of slug and pellet injuries.

Shotgun slug injuries have received little attention while shotgun pellet wounds have been well described. Twenty-two shotgun pellet and 13 shotgun slug injuries treated over a 14-year period were retrospectively reviewed. Extremity and thoracic wounds were most frequent in both groups. The incidence of vascular and nerve injuries was similar for slug and pellet wounds. Angiography was more often used to evaluate pellet wounds for vascular disruption. The rate of wound infection was 38% for slug wounds versus 32% for pellet injuries. Tissue grafting was more frequently necessary for reconstruction after pellet injury. Long-term disability was documented in 15% of patients with pellet wounds and 23% with slug wounds. Despite similarities in wound location and outcomes, the ballistic differences between shotgun slugs and pellets resulted in significant differences in wounding characteristics and extent of injury which have important ramifications in management.

Image-guided or needle-localized open biopsy of mammographic malignant-appearing microcalcifications?

BACKGROUND: The evaluation and initial management of abnormalities detected on screening mammography have evolved substantially over the last decade. This study was designed to evaluate the most appropriate initial diagnostic biopsy technique for patients presenting with malignant-appearing microcalcifications on screening or diagnostic mammography. STUDY DESIGN: An institutional review of a prospective database was performed to compare initial image-guided breast biopsy (IGBB) and needle-localized open biopsy (NLOB) in patients presenting with malignant-appearing microcalcifications. Patients with atypical hyperplasia (AH) or carcinoma in situ (CIS) were identified and reviewed separately. Measures of outcomes included the total number of procedures, time from initial biopsy to definitive treatment, charges, and percentages of patients who required both procedures. RESULTS: A total of 17,121 patients underwent mammography from July 1994 to December 1996 at Gundersen Lutheran Medical Center. Indeterminate microcalcifications were found in 167 patients and were the reason for IGBB in 112 and NLOB in 55 patients. Histologic results included 81 patients (48%) with benign lesions, 25 (15%) with invasive cancers, and 61 (37%) having a proliferative finding including AH or CIS. Ductal CIS was present in 42 (72%) of the 61 proliferative lesions. Comparisons were made between the groups of patients with CIS or AH who underwent initial NLOB (n = 25) versus those having initial IGBB that was followed by a secondary NLOB (n = 25). The median elapsed time to definitive therapy was 20 days (range 0 to 336 days) for initial IGBB followed by NLOB and 7 days (range 0 to 79 days) for an initial NLOB performed for suspicious microcalcifications (p = 0.0367). The total number of procedures performed on each patient and total costs were also less for patients having an initial NLOB. CONCLUSIONS: The time to definitive local therapy, the number of procedures, and overall charges were less for patients with AH or CIS having initial NLOB as opposed to initial IGBB. Careful initial evaluation of microcalcifications may identify some patients for whom an initial NLOB remains the most appropriate procedure. Such patients desiring breast-conserving therapy may benefit in terms of time to definitive treatment, total number of procedures performed, and cost if a careful NLOB is the initial procedure performed as a formal lumpectomy.

Nonoperative management of splenic injury: are follow-up computed tomographic scans of any value?

OBJECTIVE: To determine the value of follow-up abdominal computed tomography in patients with splenic trauma managed nonoperatively. DESIGN: Retrospective chart review. MATERIALS AND METHODS: A total of 108 consecutive patients with splenic injuries treated at a single institution from 1990 to 1996 were studied. All admission and follow-up computed tomographic (CT) scans were reviewed by the authors. RESULTS: Initial management was surgical in 35 patients (32%) and intentionally nonoperative in 73 patients (68%). Nonoperative management was successful in 45 of 49 adults (92%) and 21 of 24 children(88%). Sixty-two follow-up abdominal CT scans were obtained in 49 patients. Information that affected management was evident on only one follow-up CT scan performed in the absence of clinical indications. Potential savings in hospital and physician charges for routine follow-up CT scans in this study were $54,302.00. CONCLUSIONS: Follow-up abdominal CT scans are not routinely necessary in patients with splenic injuries managed nonoperatively.

Management of thyroid cancer of follicular cell origin: Gundersen/Lutheran Medical Center, 1969-1995.

BACKGROUND: Most reports regarding the treatment of thyroid cancer originate from university referral centers. In this article, we report our experience in managing thyroid cancer of follicular cell origin at a non-university institution over a 26-year period. STUDY DESIGN: We reviewed the medical records of all patients treated for thyroid cancer at the Gundersen/Lutheran Medical Center from 1969 to 1995. Histologic types, demographic and clinical characteristics, laboratory results, treatment, complications, and followup observations were tabulated. Risk was assigned according to the age, presence of distant metastasis, extent of the primary tumor, and site of the primary tumor (AMES) staging system. RESULTS: The histologic classification was as follows: papillary, 139; follicular, 24; Hürthle cell, 14; and anaplastic, 11. Low-risk lesions were identified in 96%, 79%, and 71% of the patients with papillary, follicular, and Hürthle cell (collectively designated differentiated) carcinoma, respectively. We treated 60% of our patients with differentiated thyroid cancer with near-total or total thyroidectomy. Clinically involved cervical lymph nodes were removed singly or by modified neck dissection. We frequently ablated thyroid remnants after operation with 29.9 mCi (1,110 MBq) of 131I, after which we treated the patient with suppressive doses of levothyroxine. Patients were evaluated yearly with thyroglobulin measurements and, in some high-risk patients, with total-body 131I scans. Cancer recurred in 13%, 8%, and 7% of our patients with papillary, follicular, and Hürthle cell carcinoma, respectively. Only three patients died of differentiated thyroid cancer; eight are alive with malignancy. In anaplastic thyroid cancer, cervical lymph node metastases, local invasion, and distant metastases were present in 18%, 64%, and 45% of patients at the time of initial evaluation. Total or near-total thyroidectomy was possible in only four of nine patients treated surgically. External radiation (11 patients) and chemotherapy (two patients) were used. Additional metastases developed in 45% of the patients, and nine patients died within a year. Permanent hypoparathyroidism or hoarseness complicated 2.7% of the thyroid operations. CONCLUSIONS: Although our followup was relatively short, the results of treating thyroid cancer by general surgeons at a nonuniversity hospital compare favorably with results obtained from university referral centers.

Spectrum of general surgery in rural America.

OBJECTIVES: To define the types of surgery performed by rural surgeons, to compare their experience to that of graduating US surgical residents and to document rural surgical mortality. DESIGN: Prospective registry of consecutive cases recorded by 7 rural general surgeons working in one department of surgery from December 31, 1994, through March 30, 1996. Comparison with the 1995 Report C (Resident Operative Logs) of the Residency Review Committee. National survey of surgical residency programs regarding formal gynecology experience. SETTING: Nine rural community hospitals in the Midwest. PATIENTS: Patients undergoing surgery in 9 cities with populations of fewer than 10000. MAIN OUTCOME MEASURES: Type of surgery and postoperative (30-day) mortality. RESULTS: Two thousand four hundred twenty procedures were performed by 7 surgeons practicing in 9 cities with populations of 1500 to 8000. There were 6 (0.25%) postoperative deaths. Case types are as follows: endoscopy, 686 (28.3%); gynecology, 498 (20.6%); hernia, 241 (10%); colorectal, 194 (8%); biliary, 183 (7.6%); cesarean sections, 130 (5.4%); breast, 129 (5.3%); orthopedic, 115 (4.8%); carpal tunnel, 63 (2.6%); otolaryngology, 35 (1.4%); and endocrine, 1 (0.4%); for a total of 2420 (100%). Report C indicated 1995 graduating chief residents averaged 8 obstetric and and gynecologic and 5.3 orthopedic cases during their residency. Of 204 surgical residency programs surveyed, 106 (52%) offered no obstetrics and gynecology rotation. CONCLUSIONS: A large volume of surgery was performed with low mortality by 7 rural general surgeons. The operative experience of 1995 residency graduates differed from our rural surgeons. We recommend a rural surgical track in selected training programs to prepare graduates better for rural practice. Senior level rotations in endoscopic, gynecologic, obstetric, and orthopedic surgery and mentorship with rural surgeons would be optimal.

Functional outcome after incomplete spinal cord injuries due to blunt injury.

During a 3-year period, 19 patients with incomplete spinal cord injuries caused by blunt trauma were admitted to a single rural referral centre. The mean age was 50 years. Injury mechanisms included falls in eight, road traffic accidents in five, diving mishaps in two, and miscellaneous in four. The level of spinal cord injury was cervical in 11, thoracic in five, and thoracolumbar in three. Initial management included a standard high-dose methylprednisolone protocol for 24 h after injury in eight patients treated since May, 1990. Neurosurgical procedures were performed in 11 patients. There were three deaths, all in patients over 75 years of age with pulmonary complications. Of 16 survivors, 10 demonstrated significant functional neurological improvement by the time of hospital discharge, and 11 by late follow up. Complete recovery occurred in five of the survivors. Complications occurred in 11 patients, including pulmonary (nine), infectious (six), and gastrointestinal (three), but could not be associated specifically with the high-dose steroid protocol. In conclusion, incomplete spinal cord injuries after blunt injury were relatively uncommon in this setting. No significant increase in complications was observed after institution of the high-dose methylprednisolone protocol in May, 1990. However, pulmonary, gastrointestinal, and infectious complications were common. Of the 16 survivors, 11 demonstrated significant functional improvement. Mortality appeared to be related to advanced age and to pulmonary complications.

Analytical procedures for estimating milk intake and yield in steady-state and nonsteady-state systems.

A tracer method for determining milk intake, introduced earlier, was based on the transfer of tritiated water from a lactating female to a nuring offspring via milk. The analysis of the tracer data assumed a steady state system, i.e., the total body water of the offspring was assumed to be constant over the measurement period. This paper discusses the potential errors in the milk intake estimates in applications where steady-state does not exist. Three analytical procedures are considered and include the application of 1) steady state equations for a nonsteady-state system, 2) analytical solutions to nonsteady-state equations, and 3) a computer modeling program, SAAM-27. The application of steady-state equations is the simplest procedure and may yield acceptable estimates if the growth rate of the nuring offspring is low. The analytical solution procedure yields acceptable estimates at high growth rates of the nursing offspring but becomes unacceptable at low growth rates. The SAAM program requires sophisticated computer hardware and programming; however, the procedure yields the best estimates of milk intake in applications ranging from steady-state to high growth rates.

Hand position as a variable determining the accuracy of aiming movements.

Two experiments investigated the effect of hand position on the accuracy of short- and long-duration aiming movements in the presence and absence of visual feedback. In Experiment 1 (N = 16) short aiming movements were executed rapidly, which would require them to be predominantly programmed, whereas in Experiment 2(N = 8) these movements were performed slowly enough so that visual feedback, which implies that they were predominantly programmed. However, the long-duration, short-length movements of Experiment 2 were disrupted when visual feedback was removed, which suggests that these movements were being guided by visual feedback. Having the heel of the responding hand in contact with the target platform during the response resulted in greater accuracy than no hand contact for the short-length movements of both experiments. Taken together, these results indicated that hand contact produced greater aiming accuracy than no hand contact for both programmed- and feedback-based movements.