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Biomedical subjects

R H Alexander

Publications and source records attributed to R H Alexander.

At least 19 recordsLinked to original sources
PubMed1998

Germline and somatic mutation of the gene for multiple endocrine neoplasia type 1 (MEN1).

Dideoxyfingerprinting was used to screen for germline and somatic MEN1 mutations. This method, applied to a panel of germline DNA from 15 probands with multiple endocrine neoplasia type 1 (MEN-1), allowed confident discovery of the MEN1 gene. Germline MEN1 mutation has been found in 47 out of 50 probands with familial MEN-1, in 7 out of 8 cases with sporadic MEN-1, and in 1 out of 3 cases with atypical sporadic MEN-1. Germline MEN1 mutation was not found in any of five probands with familial hyperparathyroidism. Somatic MEN1 mutations were found in 7 out of 33 parathyroid tumours not associated with MEN-1. Allowing for repeating mutations, a total of 47 different germline or somatic MEN1 mutations have been identified. Most predict inactivation of the encoded 'menin' protein. supporting expectations that MEN1 is a tumour suppressor gene. The 16 observed missense mutations were distributed across the gene, suggesting that many domains are important to its as yet unknown functions.

Codon↗
PubMed1997

Somatic mutation of the MEN1 gene in parathyroid tumours.

Primary hyperparathyroidism is a common disorder with an annual incidence of approximately 0.5 in 1,000 (ref. 1). In more than 95% of cases, the disease is caused by sporadic parathyroid adenoma or sporadic hyperplasia. Some cases are caused by inherited syndromes, such as multiple endocrine neoplasia type 1 (MEN1; ref. 2). In most cases, the molecular basis of parathyroid neoplasia is unknown. Parathyroid adenomas are usually monoclonal, suggesting that one important step in tumour development is a mutation in a progenitor cell. Approximately 30% of sporadic parathyroid tumours show loss of heterozygosity (LOH) for polymorphic markers on 11q13, the site of the MEN1 tumour suppressor gene. This raises the question of whether such sporadic parathyroid tumours are caused by sequential inactivation of both alleles of the MEN1 gene. We recently cloned the MEN1 gene and identified MEN1 germline mutations in fourteen of fifteen kindreds with familial MEN1 (ref. 10). We have studied parathyroid tumours not associated with MEN1 to determine whether somatic mutations in the MEN1 gene are present. Among 33 tumours we found somatic MEN1 gene mutation in 7, while the corresponding MEN1 germline sequence was normal in each patient. All tumours with MEN1 gene mutation showed LOH on 11q13, making the tumour cells hemi- or homozygous for the mutant allele. Thus, somatic MEN1 gene mutation for the mutant allele. Thus, somatic MEN1 gene mutation contributes to tumorigenesis in a substantial number of parathyroid tumours not associated with the MEN1 syndrome.

Chromosomes, Human, Pair 11↗
PubMed1991

The reliability of physical examination in the evaluation of penetrating extremity trauma for vascular injury: results at one year.

All cases of penetrating extremity trauma (PET) seen at an urban trauma center were prospectively studied to determine the accuracy and safety of physical examination as the sole mode of evaluation for vascular injury. All patients with PET producing obvious or "hard" signs of vascular injury underwent immediate surgery. All asymptomatic proximity wounds were observed in hospital for 24 hours before discharge to outpatient followup. Patients with non-proximity wounds were discharged immediately. Patients with shotgun wounds and thoracic outlet injuries also underwent arteriography. Of 2,674 trauma patients evaluated during the 1-year study period, 310 (11.6%) had 366 penetrating extremity wounds, most (71%) occurring in the lower extremities. Gunshots caused most (82%) of the wounds, followed by stabs or lacerations (14.5%), and shotguns (3%). Clinically occult wounds in proximity to major limb vessels were the most common (78%) category of clinical presentation, followed by asymptomatic non-proximity wounds (16%), and wounds producing hard signs (6%). There were two missed vascular injuries, both in the asymptomatic proximity group (0.7% false negatives). Every patient taken immediately to surgery for hard signs had major arterial injury requiring repair, for a 100% positive predictive value for physical examination. No mortality or morbidity were related to protocol management. These results to date support prior reports of a negligible incidence of significant vascular injury following clinically occult proximity PET, and further suggest that the overall predictive value of physical examination of PET for vascular injury approaches 100%.

Adolescent↗
PubMed1991

Nonoperative observation of clinically occult arterial injuries: a prospective evaluation.

Forty-seven patients with 50 clinically occult injuries of major arteries were studied prospectively to determine the natural history of these lesions and the safety of nonoperative management. Penetrating trauma was the predominant mechanism and lower extremity arteries were most commonly involved. The morphology of these arterial injuries included 22 cases of intimal flaps, 21 cases of segmental arterial narrowing, 6 pseudoaneurysms, and 1 acute arteriovenous fistula. There was one death as a result of unrelated causes and another three injuries operated on immediately after arteriographic diagnosis. The remaining 46 injuries were followed up nonoperatively by serial arteriography (39) or clinical examination (7) during a mean interval of 3.1 months (range, 3 days to 27 months). Complete resolution was documented for 29 injuries (63%), whereas 3 improved, 9 remained unchanged, and 5 worsened during the period of follow-up. All worsened cases involved small or occult pseudoaneurysms that subsequently enlarged and then underwent immediate surgical repair without subsequent morbidity. Because 89% of the followed injuries never required surgery, nonoperative observation appears to be a safe and effective management option for clinically occult arterial injuries.

Adolescent↗
PubMed1990

The role of antibiotic therapy in the prevention of empyema in patients with an isolated chest injury (ISS 9-10): a prospective study.

The purpose of this study was to determine the impact of an antibiotic regimen on the incidence of empyema in patients admitted with isolated chest trauma (ISS 9/10) and hemopneumothorax requiring tube thoracostomy. All patients with isolated chest trauma and hemopneumothorax (estimated ISS 9 or 10) seen in our trauma center were considered eligible for this study. Patients were excluded for the following reasons: age less than 18 years, presence of shock at the time of initial resuscitation, ongoing antibiotic therapy for unrelated disease, documented pre-existing infection or documented abnormal immune status. Ninety patients were randomized to two treatment limbs: antibiotics and tube thoracostomy or tube thoracostomy alone. All patients had the procedure performed in the trauma center in a standard fashion. Wound care and tube care were identical. Antibiotic therapy consisted of a first-generation cephalosporin (cefazolin), one dose given just before the procedure and then q 6 h into the tube removal. Injury Severity Scores were established as described by Schwab after the manner of Baker. Statistical analysis was performed using Fisher's exact test of binary outcome. In this study, antibiotics were able to reduce the incidence of empyema in patients with isolated chest trauma and for such patients antibiotic treatment appears justified. Further work is required to determine the effect on patients with more severe injury and multisystem involvement.

Adult↗
PubMed1990

New perspectives on the management of penetrating trauma in proximity to major limb arteries.

Current management of penetrating injuries in the proximity of major extremity arteries with no evidence of vascular trauma remains controversial. A total of 318 such injuries in 254 patients were evaluated prospectively to clarify the appropriate timing and role of arteriography, as well as the natural history of these injuries. The arteries at risk were: axillary, 47; brachial, 57; superficial femoral, 176; and popliteal, 38. No deaths occurred, and no morbidity resulted from arteriographic delay of 6 to 24 hours after injury. Of the 48 arteriographic abnormalities detected, 16 involved noncritical branch vessels. There were 32 injuries to major arteries (10.0%), including localized narrowing (n = 13), intimal flap (n = 12), false aneurysm (n = 6), and arteriovenous fistula (n = 1). Shotgun wounds led to a greater arterial injury rate (3/17; 17.6%) than did gunshot wounds (24/247; 9.7%) or stab wounds (5/54; 9.3%). At the surgeon's discretion, three injuries underwent immediate exploration (one negative), whereas the remaining 29 vessel injuries were followed up nonoperatively by repeat arteriography (n = 22) or clinical examination (n = 7), for a mean interval of 2.8 months. Fifteen abnormalities resolved, 10 improved or remained unchanged, and 4 worsened. The four lesions (13.7%) that worsened (two shotgun and two axillary artery injuries) were identified within 3 months of injury and repaired surgically with no morbidity. In conclusion, only 6 operations were required out of 3218 potential injuries (1.8%), suggesting that routine arteriography is not a cost-effective means of evaluating these injuries.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1989

The natural history of clinically occult arterial injuries: a prospective evaluation.

Nineteen patients with 20 clinically occult arterial injuries were prospectively followed without surgery in order to define the natural history of these lesions. The patients were predominantly male (74%), with a mean age of 31 years. The mechanism of injury was penetrating in 13 cases and blunt in seven cases. The arterial injuries were located in the lower extremity (45%), upper extremity (35%), neck (15%), and abdominal aorta (5%). Neurologic trauma (55%) and musculoskeletal trauma (40%) were the most common associated injuries. There was no clinical manifestation of vascular injury in any case. All lesions were identified by arteriography, which was performed for high-risk blunt trauma and proximity of penetrating wounds to major vessels. Intimal flap was the most commonly demonstrated form of injury (65%), followed by focal narrowing (30%) and false aneurysm (5%). Followup of 19 injuries (95%) was obtained for periods ranging from 3 days to 19 months (mean, 3.8 months). Arteriographic followup was obtained in 15 cases (79%). One injury (5%), a false aneurysm, enlarged after 10 weeks and was surgically repaired without clinical sequelae. All other lesions either resolved (53%), improved (16%), or remained unchanged (26%). These results suggest that nonoperative observation may be a safe and feasible method of managing clinically occult arterial injuries.

Adult↗
PubMed1989

A reassessment of the role of arteriography in penetrating proximity extremity trauma: a prospective study.

Penetrating proximity extremity trauma (PPET) was prospectively studied to clarify the role of routine arteriographic evaluation (AG). Over a 24-month period, 135 patients were identified with 152 injuries from PPET. All patients underwent AG and were randomized to either immediate or delayed timing. There were 27 arteriographic abnormalities from these 152 wounds, of which 16 (10.5%) were in major arteries. One acute arteriovenous fistula underwent immediate surgery. The remaining 15 major vessel injuries were nonoperatively observed, including seven cases of segmental arterial narrowing, six intimal flaps, and two small pseudoaneurysms (one of which enlarged and underwent surgical repair after 10 weeks of followup). Nine of the remaining 14 lesions resolved; two improved and three remained clinically unchanged over a mean followup interval of 2.7 months. Shotgun trauma was the mechanism which carried the greatest risk of significant vascular injury. Although "soft" clinical signs were significantly more predictive of vascular injury following PPET than proximity alone (p less than 0.0005), 50% of all injuries to major arteries did not manifest soft signs. No extremity morbidity resulted from delayed AG or from vascular injury management. We conclude from our study population: 1) the natural history of clinically occult arterial injuries was predominantly benign; 2) AG could be safely delayed up to 24 hours; 3) "soft" signs were not clinically useful predictors of vascular injury; and 4) with the exception of shotgun wounds, AG did not appear to be a cost effective screening modality, since detection of a single vascular injury requiring surgery cost $66,420.00.

Angiography↗
PubMed1989

Penetrating injury of the vertebral artery: a unique management approach.

We have reported a case of traumatic vertebral artery transection discovered during an emergency neck exploration for penetrating injury with acute hemorrhage. Knowledge of the surgical anatomy of this vessel and awareness of the treatment alternatives that must be considered for its acute injury are important. A cooperative approach between the surgeon, anesthesiologist, and radiologist in this case, using a combination of anesthetic hypotension, surgical tamponade, and angiographic embolization, resulted in a successful outcome in this difficult case.

Adult↗
PubMed1989

Seizure disorders and trauma.

The prevalence of seizure disorder diagnosis in the general population is between 0.5% and 2.0%. Seizures may be manifested by abnormal motor activity, loss of muscle tone, and changes in mental status. Seizure may increase an individual's risk for traumatic injury by adversely influencing performance in a particular situation. We identified 30 patients admitted to our trauma service over a three-year period with injury related to seizure; 16 were male and 14 were female, with a mean age of 34.8 years. Twenty-eight patients (93%) had a history of seizure activity, with the mean duration of seizure activity of 16.5 years (range, three to 40 years). Both seizure diagnosis and etiology were multifactorial. Multiple drug therapy predominated, phenytoin (Dilantin) being the most frequently used medication. Overall compliance was poor (53%). Only blunt injury occurred in these patients, 50% suffering injury from falls. Injuries from motor vehicle accidents (40%) were the next most frequent (auto crash in seven cases, motorcycle crash in four, and bicycle crash in one case). The remainder of the injuries were burns (10%). Nine patients (30%) required operation. Skeletal injuries predominated (67%). Patients with a history of seizure will be frequently encountered by physicians of all specialties. The patients likely to be at increased risk for injury are noncompliant, have breakthrough seizures (ie, despite therapy), or have the metabolism of their seizure medication altered by alcohol or other drugs. To prevent potentially serious injury, these patients should be identified and counseled.

Accidental Falls↗
PubMed1989

The 1983 Beirut Airport terrorist bombing. Injury patterns and implications for disaster management.

The casualty profile and results of the medical care provided for the survivors of the terrorist truck bombing of the U.S. Marine Corps facility in Beirut, Lebanon, in 1983 were reviewed to determine the factors that influenced casualty survival. This explosion resulted in 346 casualties, of whom 234 (68%) were immediately killed. The spectrum of injury was determined in 85 survivors using the Injury Severity Score (ISS). There were seven (6.3%) deaths among the 112 immediate survivors. All deaths occurred among the 19 (17%) victims who were critically injured (ISS greater than 15), giving a mortality in this population of 37 per cent. Six (86%) of the seven deaths were associated with an initial delay in treatment. Head injury was the most common fatal injury among both immediate fatalities (71.4%) and immediate survivors (57%). Thoracic injury and burns each accounted for 29 per cent of survivor deaths. Triage efficiency, as determined by the rates of overtriage (80%) and undertriage (0), did not appear adversely to affect mortality. Critical analysis of disasters such as this can contribute to improvements in preparation and casualty care in the event of future disasters.

Disasters↗
PubMed1988

Penetrating trauma to the buttock.

Penetrating trauma to the buttock is an injury with potential impact on multiple body systems. The purpose of this study was to review our experience with penetrating trauma to the buttock, to establish the frequency of system injury and related morbidity and mortality, and to make recommendations for the evaluation and management of these injuries. Among the 56 system injuries, soft tissue injuries predominated. Of the 25 operative procedures done, eight were for wound care and debridement and seven for rectal injuries; three were orthopedic, two vascular, three genitourinary, and one neurosurgical. One patient had examination under anesthesia, and one had laparotomy for missile trajectory. There were no deaths in this series. Morbidity consisted of nerve injury/defect in three patients, stroke in one patient, and impotence in one. An understanding of the systems at risk in penetrating buttock trauma is necessary for prompt multisystem work-up.

Adult↗
PubMed1984

The effect of advanced life support and sophisticated hospital systems on motor vehicle mortality.

A mileage population death index (MPDI) was devised to compare the death rate from motor vehicle trauma in Florida counties. The MPDI was defined as the average death rate per one hundred million miles driven divided by the population of the particular county X 10(5). The resultant MPDI was correlated with the presence in a county of basic life support only and advanced life support. In addition, counties with large metropolitan hospitals which might possibly classify as Level I institutions were compared with other counties. A low MPDI was found to be highly correlated with the presence of an ALS system (p = 0.001). Counties with hospitals which might qualify as Level I also had a significantly lower MPDI (p = 0.04). We conclude that the presence of advanced life support and a sophisticated hospital is correlated with a significantly lower motor vehicle mortality.

Accidents, Traffic↗
PubMed1984

Nursing intervention scoring system in management of a surgical intensive care unit.

Hospital cost containment and nursing shortages have diminished resources available in surgical intensive care units (SICU). To provide a more quantitative approach to management of these resources, the nursing intervention scoring system (NISS) devised by Greenburg et al was instituted in the SICU at the VA Medical Center, Gainesville, Fla. The NISS scores for patients in the SICU were calculated without computer support. During a four-month study period, 725 NISS evaluations on 70 patients were collected. Characteristic curves of NISS scores versus postoperative days were generated from the data and were predictive of workloads in the unit. In addition, NISS patient scores provided a basis for day-to-day bed control and provided an effective tool for management of nursing service staffing. The hospital administrators responded positively to quantitative documentation of SICU resource requirements by providing additional personnel, equipment, and intermediate care facilities. We have concluded that the NISS is an effective means of providing optimal day-to-day use of SICU beds. In addition, the NISS also provides the data needed to quantitate unit needs for nursing service and administration.

Aorta, Abdominal↗
PubMed1983

Determining the content of a surgical curriculum.

The purpose of undergraduate surgical education is to prepare the student for both the residency and eventual practice of medicine. To help determine the surgical knowledge and skills that would eventually the useful to the student, we conducted a survey of residents in training, physicians in practice, and surgical educators (department chairpersons and clerkship directors). Members of the Curriculum Committee of the Association for Surgical Education developed a questionnaire in which the respondents were asked to grade the functional importance of 84 areas of knowledge and 46 skills (0 = unnecessary, 3 = proficiency necessary). Using a modified Delphi technique to collect information, we sent the questionnaire to eight medical school graduation classes of 1975 (730 persons) and 1980 (776 persons) and all department chairpersons and/or clerkship directors (179). The results of the survey (46% response) revealed considerable agreement about the importance of certain skills and areas of knowledge, enabling us to rank order skills and knowledge based on mean responses (0.0 to 3.0). Physicians in practice, residents, and educators believed that certain areas of knowledge (e.g., acute abdominal problems, appendicitis, shock, cancer of the breasts) and skills (e.g., history taking and physical examination, gowning, suture removal) were very important (greater than 2.250, while other areas of knowledge (e.g., transplantation, liver abscess, soft tissue sarcomas) and skills (e.g., insertion of Swan-Ganz catheter, abdominal paracentesis, cricothyroidotomy) were less important (less than 1.3). This approach allows us to assign priorities to areas of knowledge and skills when determining curriculum content and to include functional criteria when developing educational objectives.

Attitude of Health Personnel↗
PubMed1982

Computed tomographic diagnosis of acute aortoiliac catastrophes.

Whole-body computed tomography (CT) was used as an initial examination in stable patients whose symptoms were suggestive of aortoiliac emergencies. In three cases, CT provided highly specific diagnoses in three different aortoiliac complications. Computed tomography proved to be a fast and reliable diagnostic tool in emergency settings.

Aged↗
PubMed1982

Revascularization of kidneys with totally occluded renal arteries.

Nephrectomy has been the accepted treatment for renovascular hypertension due to an occluded renal artery but successful revascularization of occluded renal arteries has resulted in partial return of function and relief of hypertension. We performed aorticorenal bypass operations on four patients whose renal arteries were not patent. One graft failed immediately, two remained open for four to six months, and one is functioning at two years. In 70 other cases in which totally occluded arteries were revascularized, the overall patency rate was 96%. Hypertension was relieved for controlled in 77%.

Aged↗