Occult fever in surgical intensive care unit patients is seldom caused by sinusitis. Febrile intensive care unit (ICU) patients were evaluated prospectively for sinusitis. Of 598 admissions, 26 patients with transnasal cannulas, ICU stays over 48 hours, and occult fevers were identified. These 26 underwent physical examinations and sinus computed tomographic (CT) scans. Maxillary centeses and cultures were done in patients with CT abnormalities. Patients with positive scans had nasal tubes removed and received decongestants. Scans were abnormal in 19 (73%). All patients with major CT changes had positive maxillary taps. Most infections were polymicrobial; enteric bacilli were common. Fever resolved with nonoperative care in 18 (95%) patients; in only 1 patient was fever primarily from sinusitis. Sinus CT scans are often abnormal in ICU patients with occult fevers and transnasal cannulas. Pneumatic otoscopy can serve as a screening tool. Most patients respond to nonoperative management. Remote infections are often present. Although radiographic nosocomial ICU sinusitis is common, it is seldom the sole source of fever or the proximate cause of significant morbidity.


Are modified radical mastectomies done for T1 breast cancers because of surgeon's advice or patient's choice? Clinical trials show that T1 breast cancers are equally well treated with breast-conserving surgery as with modified radical mastectomy. However, the Colorado Central Cancer Registry indicates that, for the past 5 years, the majority of women (72%) with T1 breast cancer in Colorado have undergone modified radical mastectomies. A questionnaire was sent to 175 general surgeons to determine the reasons for the high number of modified radical mastectomies still being performed. The results indicate that one group of surgeons (34% of those responding) believes each type of surgery has equal survival rates but unknowingly influences the patient to choose modified radical mastectomy, with a subtly biased presentation. Education of both surgeons and patients is needed to increase the number of patients with T1 breast lesions who can benefit from breast-conserving therapy.


Risk of major elective operation after myocardial revascularization. Although an increased surgical risk of ischemic myocardial disease is widely accepted, amelioration of this risk after coronary artery bypass is poorly defined. We compared the outcomes of major elective general and peripheral vascular operations in 181 patients with prior coronary artery bypass grafting (CABG) with outcomes in an age-, gender-, and procedure-matched group without prior CABG (NOCABG). Despite the perception of a greater operative risk in the CABG patients (more CABG patients in American Society of Anesthesiologists [ASA] class III and fewer in ASA class I, p < 0.001), mortality (1.1% CABG versus 2.8% NOCABG) and morbidity (18.8% CABG versus 18.5% NOCABG) rates in the two groups were not significantly different. For patients who have undergone successful CABG, it appears that: (1) the risk of subsequent elective major general and vascular surgical operations is similar to that of an age-, gender-, and procedure-matched cohort, and (2) the mortality rate after elective operations is low.


Advantages of the Papillon protocol in the preoperative treatment of rectal carcinoma. Standard treatment for advanced rectal carcinoma currently includes surgery, radiotherapy, and chemotherapy. Although there are theoretic advantages to preoperative irradiation, it is often not performed because of the prolonged delay of surgery and the purported increase in perioperative complications. A pilot study was undertaken at our institution to evaluate a treatment protocol advocated by Dr. Papillon that offers a shorter treatment time and less patient morbidity than conventional preoperative therapy for rectal carcinoma. Twenty patients with rectal cancer underwent the preoperative regimen that consisted of 3,000 cGy delivered in 10 fractions over 12 days with concomitant 5-fluorouracil and mitomycin-C. Complications were acceptable. Local recurrence was lower than in most reported trials, and survival rates were comparable. Additional benefits of the protocol include lower radiation morbidity to the patient and a decreased delay between diagnosis and surgery.


Virulent diverticular disease in young obese men. Recent treatment of young patients (aged 40 years or less) with complicated diverticulitis prompted us to review our experience. During a 9-year period ending in December 1990, 61 of 238 patients treated for acute diverticulitis were 40 years of age or younger. The younger patients were primarily obese Hispanic males in whom the correct diagnosis was frequently missed. Younger patients more frequently required an operation on an urgent basis for complications of diverticulitis during the initial hospitalization. The most common indication for operation in young patients was perforation compared with recurrent disease for the older age group. The younger group had a sevenfold incidence of enteric fistulas complicating their acute episode of diverticulitis. Our data suggest that diverticular disease in young patients is more common and more likely to require early surgical intervention than previously noted. In addition, obesity may represent an important etiologic factor in the development of diverticular disease.


Reoperation in patients with the short bowel syndrome. The clinical courses of 53 adult patients with the short bowel syndrome (SBS) were evaluated to determine the incidence of and indications for reoperation. Mesenteric vascular disease (23 patients) and malignancy/irradiation (18 patients) were the most frequent causes of resection. Early reoperation was necessary in nine (17%) patients, primarily for intestinal complications. Twenty (53%) of the 38 patients leaving the hospital required a later abdominal procedure during the mean follow-up of 30 months (range: 2 to 108 months). Three (33%) of nine patients with ulcer disease had gastric resection. Six (21%) of 28 patients at risk for cholelithiasis developed symptoms. Four of these patients underwent cholecystectomy, and three others had a prophylactic cholecystectomy. Ten patients underwent ostomy closure or formation. Intestinal disease necessitated stricturoplasty (three), serosal patch (one), minimal resection (three), or takedown of an ileal conduit (one). Twenty-four (63%) of 38 patients with SBS received home total parenteral nutrition for a mean of 22 months (range: 2 to 105 months). Eleven patients required more than 1 vascular access procedure, and 4 had more than 3 procedures. Patients with the SBS frequently require reoperation for intestinal conditions, cholelithiasis, peptic ulceration, and vascular access. Prophylactic cholecystectomy and strategies for preserving intestinal length are important considerations in these patients.


A case-control study of late recurrence of malignant melanoma. Late recurrence of malignant melanoma is uncommon but appears to be a growing problem. It is unclear whether late recurrence has a better prognosis than early recurrence. Since the answer may influence treatment, we compared recurrence sites and subsequent survival in 35 patients with disease-free intervals of 72 to 240 months (median: 127 months) with 35 case-controls who had relapse at 4 to 56 months (median: 26.7 months). The distribution of recurrence sites in early relapse was 66% in regional nodes or soft tissue and 34% in distant soft tissue or viscera. In late relapse, this distribution was 49% in regional nodes or soft tissue and 51% in distant soft tissue or viscera (no significant differences). Median survival for patients with early and late recurrences in regional nodes or soft tissue was 26 and 44 months, respectively (no significant differences); 5-year survival was 27% and 33%, respectively (no significant differences). Median survival was similar for early or late relapse in distant soft tissue or viscera (8 and 10 months, respectively), as was 5-year survival (0% and 6%, respectively). These results suggest that the metastatic pattern and survival after recurrence are similar for patients with early and late recurring melanoma.


Operative morbidity and risk factor assessment in melanoma patients undergoing inguinal lymph node dissection. A series of 168 patients who underwent 177 inguinal lymph node dissections from 1979 to 1989 were retrospectively reviewed to determine the incidence and severity of postoperative complications as well as the perioperative risk factors associated with them. Operative mortality was 0%, whereas the incidence of moderate to severe wound infection was 11%, skin flap problems 0%, seromas 6%, and hemorrhage 3%. The occurrence of a wound complication increased the average hospital stay from 11 to 12 days. Multivariate risk factor analysis revealed age older than 50, male sex, and smoking to be significant risk factors for developing a wound infection. The use of prophylactic antibiotics and the duration of closed suction catheter drainage were not predictive of wound complications. Overall, 44% of patients experienced some postoperative edema, with only 7% of patients having 1+ edema that lasted longer than 6 months. Combined ilioinguinal lymph node dissection increased the chance of developing moderate to severe edema. These risk factors identify patients at high risk for morbidity, which should lead to improved perioperative care.


The elderly burn patient.

The elderly burn patient. During a 16-year period, 547 patients who were older than 64 years of age with a mean total body surface area (TBSA) (third-degree burns) of 25% were treated. Etiologies were flame/flash in 81% of patients, scald in 11%, solids in 7%, and electrical/chemical in 1%. Seventeen percent of patients had significant causal factors. An inhalation injury was present in 13% of patients, and the mortality in these patients was 100%. Burn excision was performed 239 times in 165 patients. The majority of excisions were for full-thickness burns. Excision did not improve overall survival in patients with third-degree burns of 0% to 10%, but the length of stay (LOS) in excised and nonexcised survivors was improved (9 versus 21 days, respectively). The LOS and survival were not significantly different in patients with burns between 11% and 20%. Postburn complications occurred in 28% of patients. Overall mortality was 50% (mean age: 77 years; TBSA: 40%). There were no survivors with over 47% TBSA burns. The leading cause of death was pulmonary sepsis. Most surviving patients returned to a satisfactory lifestyle after discharge.


Management of blunt hepatic injuries.

Management of blunt hepatic injuries. Sixty-three consecutive patients with blunt hepatic trauma were examined. Twenty-four patients underwent immediate operation, and 39 patients were evaluated by computed tomography (CT), of whom 17 underwent operation. Ten patients had no hepatic abnormalities on CT and had operations for associated injuries. Liver injuries were noted in the remaining seven patients, but CT underestimated the injury in four patients. A large hemoperitoneum was present in all seven patients by CT, and the average transfusion was 10 U during initial resuscitation. Twenty-two patients with grade I to III injuries and a small to moderate hemoperitoneum were managed nonoperatively. Six of these patients had transfusions during resuscitation. Only one patient received more than 2 U. There were no deaths and no major complications related to the liver injury. Most patients had repeat CT at 1 week, which demonstrated stable or improving injuries. CT may underestimate the degree of liver injury. Nonoperative management is appropriate in stable patients with grade I to III injuries and a small to moderate hemoperitoneum. These patients should require no more than 2 U of blood, and repeat scans should demonstrate a stable injury.


Hematuria as a predictor of abdominal injury after blunt trauma. Among the 1,484 patients included in the Renal Trauma Project with evidence of blunt trauma and hematuria, 160 patients were found to have both hematuria and a significant intra-abdominal injury not related to the genitourinary system. The incidence of abdominal injury generally increased with the degree of hematuria, approaching 24% in patients with gross hematuria. For each category of degree of hematuria, patients with shock had a significantly higher incidence of abdominal injury (p < 0.05) than patients without shock. The incidence of abdominal injury in patients with microscopic hematuria and shock was 29%, and it was 65% for patients with both gross hematuria and shock. All patients with gross hematuria after blunt abdominal trauma and all patients with microscopic hematuria and a history of shock should be evaluated for both urologic and extra-renal abdominal injuries.


How much monitoring is needed for basilar skull fractures? Basilar skull fractures account for approximately 19% of all skull fractures. There have been little data published concerning the need for intensive care monitoring in this injury. We retrospectively studied 259 patients admitted to our trauma center over an 8-year period with a diagnosis of basilar skull fracture. All patients were evaluated with cranial computed tomographic (CT) scans. These patients were admitted to the trauma service, and neurosurgical consultation was obtained in all cases. The diagnosis was made by clinical signs in 207 patients (80%), by CT scan in 47 (18%), and by plain films in 5 (2%). Ninety-two patients (group I) had intracranial pathology in addition to basilar skull fracture. Twenty-one patients in this group underwent craniotomy. In this group, the morbidity and mortality rates were 11% and 7%, respectively. Forty-four patients (group II) had no intracranial pathology and a Glasgow Coma Score (GCS) of less than 13. The morbidity was 2%, and the mortality was 2%. One hundred twenty-three patients (group III) had no intracranial pathology on CT scan and a GCS of 13 or greater. The complication rate in this group was 1%, and there was no neurologically related mortality. Patients who are admitted with a diagnosis of basilar skull fracture and who have a GCS of 13 or greater with no intracranial pathology on CT can be managed without intensive care monitoring.


What are the contraindications for laparoscopic cholecystectomy? Acute cholecystitis, morbid obesity, and previous upper abdominal surgery have been reported as relative contraindications to laparoscopic cholecystectomy. An analysis of 706 laparoscopic cholecystectomies performed at our institution was undertaken to determine if these relative contraindications led to increased morbidity, an increased rate of conversion to the open technique, or longer operating time. One hundred ninety-seven patients demonstrated one or more relative contraindications to laparoscopic cholecystectomy. Morbidity was not increased in patients with these risk factors, but conversion to open cholecystectomy was required in a greater percentage of patients with acute cholecystitis. We favor an attempt at laparoscopic cholecystectomy in patients with these risk factors; however, they should be counseled as to the increased risk of conversion to open cholecystectomy in the presence of acute cholecystitis.


Parathyroid pathology in an intrathyroidal position. A systematic approach based on the embryology of the parathyroid glands should allow for the appropriate identification of both normal and abnormal glands at the time of parathyroidectomy. The exact role of subtotal thyroidectomy as part of this approach remains in question because of the low incidence of intrathyroidal adenomas reported in the past. From 1978 to 1992, 97 cervical explorations were performed in 96 patients (mean age: 56 years) with hyperparathyroidism. Four patients (4%) were found to have intrathyroidal parathyroid adenomas and were cured by ipsilateral partial or subtotal thyroid lobectomy on the side of a missing gland. One parathyroid adenoma completely replaced the right lobe of the thyroid, whereas two inferior and one superior intrathyroidal adenomas were found in the remaining three patients. The 4% incidence of intrathyroidal adenomas is higher than that reported in most series and suggests that this entity may be a more common cause of failed parathyroid explorations than is currently thought. Ipsilateral thyrotomy or subtotal thyroid lobectomy continues to be a potentially curative procedure for hyperparathyroidism when there is a missing and presumably diseased superior or inferior gland.


Efficacy of selective intrabronchial air insufflation in acute lobar collapse. Flexible fiberoptic bronchoscopy (FFB) to remove mucous plugs followed by selective intrabronchial air insufflation (SII) to expand the atelectatic lung was used in 17 surgical intensive care unit (SICU) patients with pulmonary lobar collapse. Thirteen patients were admitted for acute trauma, and the remainder were elderly postoperative patients. Lobar collapses occurred on SICU days 1 to 18 (mean +/- SEM: 5 +/- 1 days), and duration ranged from 4 to 258 hours (mean: 77 +/- 18 hours). Indications for FFB with SII included critical hypoxemia in 5 patients, worsening collapse in 2, and failure to respond to aggressive respiratory care in 10 (59%). FFB with SII was effective in 14 (82%) patients: 10 achieved full lung re-expansion, and 4 partial lung re-expansion. When lobar collapse was of less than 72 hours' duration, 92% (12 of 13) of patients had lungs re-expanded compared with 50% (2 of 4) whose collapse existed for more than 72 hours. The mean PaO2/FIO2 (fraction inspired oxygen) ratio was 135 +/- 18 prior to FFB with SII and increased to 205 +/- 21 after FFB with SII. Complications were minor and clinically insignificant. In conclusion, SII appears to be a simple, safe, effective adjunct to FFB in the treatment of SICU patients with pulmonary lobar collapse.


Contribution of routine intraoperative completion arteriography to early infrainguinal bypass patency. To determine the clinical utility of routine intraoperative completion arteriography, we prospectively evaluated 214 consecutive infrainguinal bypass grafts (209 reversed-vein and 5 polytetrafluoroethylene grafts) performed from July 1987 to August 1991. Visual inspection, pulse palpation, and continuous-wave Doppler examination were performed in all cases. At least 1 completion arteriogram was obtained in 213 cases (99%). The bypasses were to the popliteal artery in 130 cases and to the tibial or pedal arteries in 84 cases. Graft patency was confirmed at 30 days in all patients by ankle-brachial index determinations (greater than 0.2 increase) and duplex scan-derived peak-systolic flow velocities (greater than 45 cm/s). Significant technical problems requiring revision were identified in 18 grafts (8%), including 6% of popliteal grafts and 12% of tibial/pedal grafts. Only three of these problems were suspected by pulse palpation or continuous-wave Doppler examination. The intraoperative angiographic findings leading to revision included distal anastomotic stenoses (n = 6), distal arterial disease requiring sequential bypass (n = 4), mid-graft valvular or branch ligature stenoses (n = 4), distal arterial thrombosis (n = 2), and graft kink or twist (n = 2). Thirty-day primary patency was 99% (129 of 130) for femoropopliteal grafts and 93% (78 of 84) for femorodistal grafts. Secondary patency was 100% (130 of 130) and 96% (81 of 84), respectively. Primary patency was 89% (16 of 18) for those grafts that required intraoperative revision based on arteriographic findings. We conclude that routine completion arteriography is an excellent method of ensuring the intraoperative technical adequacy of infrainguinal bypass. The test is easy to perform, reproducible, and should be considered the "gold standard" for intraoperative bypass assessment. Prior to adopting angioscopy or duplex scanning for intraoperative surveillance, randomized, controlled validation studies against angiography should be performed.


Effect of surgical manipulation of polytetrafluoroethylene grafts on microstructural properties and healing characteristics. The effects on graft healing of alterations in the microstructure of polytetrafluoroethylene (PTFE) grafts induced by surgical instruments have not been fully elucidated. This study evaluates changes in the structural and physical properties of PTFE grafts resulting from the intentional application of commonly used surgical instruments and the influence of these changes on cellular ingrowth. The extent of cellular ingrowth into intact (10, 30, and 60 microns unreinforced and 30 microns reinforced [R]) and structurally compromised PTFE grafts (30 reinforced and 60 microns nonreinforced) implanted subcutaneously in Sprague-Dawley (n = 14) rats was evaluated at 7 and 21 days. The thrombogenicity of 10-, 30-, 60-, and 80-microns intact graft segments was determined gravimetrically after suspension in the internal jugular vein of dogs for 90 minutes. Cellular ingrowth consisting of fibroblasts, macrophages, and microvessels was directly related to porosity and was most extensive in 60-microns uncompromised graft segments, being 7-, 17-, and 20-fold greater than was observed in 60- and 30R-microns compromised grafts and undamaged 10-microns grafts, respectively. There was a direct relationship between porosity and thrombogenicity of intact graft segments suspended in the jugular vein. The amount of thrombus adherent to 80-microns graft segments was eightfold greater compared with 10-microns grafts. Manipulation of PTFE with surgical instruments significantly impairs healing and may be a possible etiologic factor in the poor long-term performance of these grafts.


Vascular complications of the intra-aortic balloon pump. The lower extremity complications of 100 consecutive patients who required the placement of an intra-aortic balloon pump (IABP) during a 3-year period were studied. Indications for the IABP included hypotension during cardiac catheterization (33%) or coronary angioplasty (13%), hemodynamic instability after open heart surgery (35%), unstable angina (5%), and cardiac arrest (14%). The incidence of IABP morbidity was 29%. Complications included ischemia (25%), bleeding (2%), lymph fistula (1%), and femoral neuropathy (1%). Twenty patients required 1 or more surgical interventions for lower extremity vascular complications. The majority of patients who underwent operation (70%) had significant pre-existing arterial occlusive disease. Local femoral artery reconstruction or repair was performed in 18 patients. Two patients had adjunctive bypasses. Continued IABP support was required in four patients after treatment of complications. One patient (1%) had an above-knee amputation. Limb ischemia was treated nonoperatively by removal of the IABP in five patients. Color-flow duplex scans were useful in distinguishing hematomas from pseudoaneurysms as well as for assessing femoral artery flow. We conclude that: (1) limb ischemia remains the primary complication of the IABP; (2) pre-insertion documentation of the severity of existing peripheral arterial disease by noninvasive studies may aid in the management of subsequent acute limb ischemia; (3) femoral artery thrombectomy or endarterectomy is usually sufficient for revascularization; and (4) noninvasive color flow studies are an important diagnostic tool in the nonoperative management of limb complications.


Concentration of refluxed acid and esophageal mucosal injury. The hallmark of gastroesophageal reflux disease (GERD) is an increase in esophageal exposure to gastric juice. This exposure can result in complications such as esophagitis, stricture, and Barrett's esophagus. The aim of this study is to determine if there are specific pH exposure patterns that are associated with the development of these complications. The 24-hour esophageal pH data for 50 normal subjects and 154 patients with proven GERD were analyzed for time spent at different pH intervals. Increased esophageal acid exposure at a given interval occurred when the cumulative time of exposure exceeded the 95th percentile of that measured in the 50 normal subjects for that interval. The greatest prevalence of mucosal damage was found in the those patients with increased esophageal exposure to pH 0 to 2, corresponding to the known pKa of pepsin. This exposure was not related to a hypersecretory state. In addition, mucosal injury was associated with an increased esophageal exposure to pH 7 to 8. We conclude that mucosal injury in patients with GERD is related to the exposure time to gastric juice with a pH of less than 2 or greater than 7.


Changing clinical spectrum of spontaneous pneumothorax. The epidemiology and etiology of spontaneous pneumothorax (SP) are shifting away from the predominance of subpleural bleb disease as emphasized by most reports since that of Kjaergaard (Sweden, 1932). We conducted a retrospective review of all patients admitted to a large urban hospital with the diagnosis of SP over the past 8 years. Of 120 patients, 32 had the acquired immunodeficiency syndrome (AIDS) (group 1, 26.6%), 43 patients had classic subpleural bleb disease or chronic obstructive pulmonary disease with blebs (group 2, 35.8%), and 45 patients had nonbleb disease exclusive of AIDS (group 3, 37.5%). These three groups were studied with respect to primary success rates with differing modalities of therapy. Bilateral SP occurred in 34% of group 1 patients, 2% of group 2 patients, and 11% of group 3 patients. The in-hospital mortality was 34% in group 1 compared with 2% in group 2 and 4% in group 3. Thirty-four percent of group 1 patients had recurrent SP compared with 16% of group 2 patients and 8% of group 3 patients. This report describes the changing etiology and epidemiology of SP in a large urban hospital from 1983 to 1991 and represents the largest single-institution report of AIDS-related pneumothorax. Standardized therapy was shown to have predictably favorable results in patients with bleb disease and nonbleb disease exclusive of AIDS. SP in patients with AIDS was associated with a high mortality rate and primary treatment failure; small-bore catheters and nondrainage therapies have a very limited role in these patients.


Conservative versus surgical management of chylothorax. Chylothorax is a potentially life-threatening disorder that has profound respiratory, nutritional, and immunologic consequences. Treatment for this problem is controversial, and the results have been variable. From 1985 to 1990, 29 patients (16 males, 13 females; mean age: 20.1 years; range: 5 days to 76.8 years) were diagnosed as having chylothorax (18 right, 6 left, 5 bilateral). Etiologies included surgical trauma (26) and nonsurgical trauma (3). Initial conservative treatment consisted of tube thoracostomy drainage (mean duration: 13.3 days; range: 1 to 62 days; mean total volume: 4,030 mL) and dietary modification (low-fat diet, total parenteral nutrition). This resulted in resolution of the chylothorax in 23 patients (79% success), although 2 patients died of unrelated causes while hospitalized (myocardial infarction and cardiopulmonary arrest). Five adult patients and one infant (21%) required ligation of the thoracic duct, with resolution of the chylothorax in all six (100% success). Despite successful duct closure, one infant died of respiratory failure unrelated to the operation, and one adult died as the result of a cerebrovascular accident 6 weeks postoperatively, yielding an operative mortality of 33% and an overall mortality of 14% (4 of 29). Our experience demonstrates that initial treatment of chylothorax with thoracostomy drainage and dietary modification is successful in the majority of patients and is not associated with high morbidity or mortality rates. Surgical intervention for chylothoraces that fail to respond to initial conservative measures will be required in a minority of patients but appears to be associated with a higher risk of complications.


Diffuse biliary tract injury after orthotopic liver transplantation. An unusual type of diffuse biliary tract injury after liver transplantation that is characterized by multiple intrahepatic biliary strictures, ductal dilatations, fluid collections, or intrahepatic abscesses has been identified. Over a 5-year period, a total of 10 patients (2%) developed diffuse intrahepatic biliary injury with established vascular patency and no obvious source for their biliary tract pathology. All patients received livers preserved in University of Wisconsin solution with a mean preservation time of 16 hours. This biliary tract injury was associated with the presence of severe preservation injury and Roux limb biliary reconstruction. Of the 10 patients, 5 were treated nonoperatively with multiple stricture dilations and stent placements, 3 underwent retransplantation, 1 was treated operatively with hepaticojejunostomy, and 1 died of sepsis. This study suggests that this complication appears to be related to preservation injury and that the etiology may be ischemic in origin.


Current experience with renal transplantation across the ABO barrier. Solid organ transplantation has traditionally been governed by the rules of blood group compatibility. Thus, it has been demonstrated that crossing the ABO blood group barrier generally results in hyperacute rejection. However, the A2 subtype of the blood group A is a weaker antigen. Under certain circumstances, organs from donors with blood group A2 can be transplanted across the ABO blood group barrier into recipients of O or B blood type. Since 1986, 33 patients including 24 blood group O and 9 blood group B patients received A2 (30) or A2B (3) donor kidneys. Both cadaver donor (31) and living-related grafts (2) have been undertaken. The mean follow-up since transplantation for the 21 patients with functioning grafts is 36 months, with a 67.2% current graft survival. Immunosuppression for these transplants consisted of azathioprine, prednisone, and cyclosporine, often in combination with prophylactic OKT3 or antilymphocyte globulin as protocol dictated. Special immunosuppressive protocols such as splenectomy or plasmapheresis were not used. The serum of the potential recipient was analyzed for immunoglobulin G (IgG) and immunoglobulin M (IgM) forms of antibody against A1 and A2 red blood cells. There is a strong correlation between a low (less than or equal to 1:8) anti-A1 IgG titer and both early and long-term graft function. Recipients with an IgG titer greater than 1:8 in the pretransplant serum had a much higher incidence of early graft failure. We no longer recommend transplantation of A2 kidneys into O or B recipients with a pretransplant titer of greater than 1:8 but found that recipients with low titers have graft function rates essentially equal to those of ABO-compatible patients. Patients with blood group B have, over time, lower anti-A IgG titers than do blood group O patients. In addition, the graft survival among blood group B patients is 89% compared with 58% among group O recipients. This may be due to the generally low titers found in blood group B recipients. Since instituting a policy in 1988 of not transplanting the kidney when the anti-A IgG titer is greater than 1:8, the survival in O patients is 88%. We recommend the screening of all organ donors with blood group A for the A2 subgroup and believe that transplantation can be safely and successfully performed in certain patients with blood group O or B.(ABSTRACT TRUNCATED AT 400 WORDS)


Surgical complications in solitary pancreas and combined pancreas-kidney transplantations. The benefits of pancreas transplantation (PT) must be weighed against the morbidity associated with the operative procedure and long-term immunosuppression. Over a 32-month period, we performed 73 PTs including 61 combined pancreas-kidney transplants (PKT) and 12 solitary PTs. In the PKT group, 25 reoperations were performed in 18 patients (29.5%) at a mean of 39 +/- 12 days after transplant. In the solitary PT group, 16 reoperations were performed in 8 recipients (66.7%, p = 0.03) at a mean of 87 +/- 12 days after PT (p < 0.01). In the PKT group, pancreas allograft survival was 93.4%. Vascular thrombosis resulted in the loss of two pancreas allografts. In the solitary PT group, pancreas allograft survival was 50% (p < 0.001), with 6 transplant pancreatectomies performed for either infectious (5) or vascular (1) complications. Surgical complications after PT are common (35.6% in this series), occur earlier in patients who undergo PKT, and are more frequent and morbid in patients undergoing solitary PT, especially after a previous kidney transplant. An aggressive surgical approach can lead to a high rate of pancreas allograft salvage without jeopardizing either the patient or the renal allograft.


Referred otalgia.

Referred otalgia. Referred otalgia is a challenging symptom, with the burden on the physician to identify the source. Only by careful patient history and physical examination can all causes in this extensive differential diagnosis be excluded. In the absence of primary otologic pathology, referred pain from a head and neck carcinoma must be considered foremost and ruled out.


Is biofeedback effective for chronic tinnitus? An intensive study with seven subjects. This study was developed to test the hypothesis that intensive biofeedback and relaxation training may favorably affect chronic tinnitus. Seven subjects with chronic tinnitus of moderate to severe intensity engaged in an intensive 5-month program of weekly, individual 90 minute sessions. All individuals attained a high standard of proficiency following training by a biofeedback specialist. A biofeedback unit was provided each subject for daily practice. Audiometric matching of tinnitus pitch and loudness and subjective comparisons of tinnitus loudness were conducted before and after every session. Audiometric evaluation showed no changes in tinnitus loudness. Nevertheless, all subjects gained satisfaction from the training. Three reported substantial psychological benefits in coping with tinnitus, two described moderate improvement, and two experienced modest gains. These results highlight the role of psychological factors in tinnitus management and indicate that biofeedback-relaxation training may be useful therapy for coping with stresses of tinnitus.


Neuronal ceroid-lipofuscinoses: the current status. In view of the epidemiological connotation of childhood neuronal ceroid-lipofuscinosis (NCL) as one of the most frequent progressive lysosomal diseases and neurodegenerative disorders in children, the recognition of the individual clinical forms of childhood NCL is still based on invasive diagnostic electronmicroscopy which, currently, may be applied also for prenatal diagnosis. Like other inherited disorders, the NCL group has finally also benefited from the genetic breakthroughs of localization of the genes for infantile NCL and juvenile NCL on chromosomes 1 and 16, respectively. This review concerns recent advances in morphological studies, broadening of the clinical spectrum of childhood NCL, new biochemical findings, and preliminary therapeutic results. Hereditary animal models, largely for human juvenile NCL, have been successfully employed in elucidation of the nosology of NCL, but the basic defect in human, canine and ovine NCL remains unknown.


Effects of recurrent otitis media in infancy on auditory perception and speech. Recurrent otitis media is commonly encountered in children before 3 years of age. Conductive hearing loss up to 40 dB is frequently associated with suppurative otitis media. Good hearing is believed to be critical to the development of normal language. This study was undertaken to evaluate the effect of recurrent otitis media on auditory perception and speech. The experimental group consisted of 33 children with a history of at least three episodes of acute otitis media before 2 years of age. A control group of 29 children experienced one or fewer episodes of otitis media in the first 2 years of age. At the time of investigation, all children were 8 to 10 years of age and had attended similar pre-school, kindergarten, and elementary school programs. None showed evidence of mental retardation nor behavioral or emotional disorders. Speech ability was assessed by a battery of tests specific for Slovene language. Subtests of the Wechsler Intelligence Scale for Children were used as well as the Reading and Writing Test. Auditory perception disorders were evident in 88% of children investigated who had a history of at least three episodes of otitis media by 2 years of age. Decreased auditory stimulation during the time of auditory maturation could prevent the development of these functions completely. No statistically significant differences were observed in the development of articulation. These observations underscore the importance of early management of recurrent otitis media during the first 2 years of age.


Myelination of the optic radiation in Leber congenital amaurosis. We have studied the myelination of the visual pathway by magnetic resonance imaging in seven children (aged 5 months to 16 years) with Leber congenital amaurosis. The corpus geniculatum laterale and the retrogeniculate optic radiation had a normal appearance on MRI in all patients. Therefore we conclude that normal myelination of the optic radiation, as it can be grossly assessed by MRI, can take place even with absent or greatly reduced visual sensory input.


Thyroid dysfunction after radiation therapy in head and neck cancer patients. The reported incidence of hypothyroidism following surgery and/or radiation therapy for head and neck cancer varies widely. Most patients undergo thyroid lobectomy during laryngectomy. Standard radiation treatment portals often include the thyroid gland. The insidious development of hypothyroidism may be misdiagnosed. This study examines the incidence of thyroid dysfunction in the setting of head and neck cancer therapy. Thyroid function tests were performed on 100 consecutive patients treated in the head and neck tumor clinic. Statistical inferences on proportions were made using chi-square analysis. Therapy included surgery only (10 patients), radiation therapy only (28 patients), and combined therapy (62 patients). These patients experienced thyroid dysfunction in 0%, 29%, and 45% of individuals respectively. These differences were statistically significant (P < .05). The highest rate of dysfunction (69%) was associated with patients undergoing laryngectomy and radiation therapy. When laryngectomy was not performed, thyroid dysfunction occurred in 28%. The likelihood of thyroid dysfunction after radiation therapy is high particularly when combined with surgery in which thyroid lobectomy is performed and the contralateral lobe is potentially devascularized. These results suggest that radiation therapy is a primary factor in alteration of thyroid function. We recommend that routine thyroid function testing be part of follow-up of all head and neck cancer patients.


Epileptic electroencephalographic abnormalities and developmental dysphasias: a study of 32 patients. The relationships between severe developmental dysphasias and epilepsy were analysed in 32 patients with congenital dysphasias. The mean age was 8 years 2 months; 19 of 32 had never had seizures; 9 had had occasional seizures; 4 were epileptic. Twenty-two of 32 had normal repeated standard EEGs, but 10 (2 of which never had seizures) showed epileptic interictal discharges. During prolonged EEG after sleep deprivation, epileptic abnormalities were observed in 13 of the 32 cases (4 of which never had seizures). The overall night sleep recordings showed epileptic abnormalities in 30 of the 32 cases (17 of which had never had seizures). The epileptic interictal abnormalities varied considerably in intensity and aspect in the same patient from one examination to another. Developmentally aphasic children show a higher incidence of abnormal EEG than expected, particularly during overall night recordings. In most cases, the physiopathology of the language disturbance might be identical to that in Landau-Kleffner syndrome.


Serum creatine-kinase-BB concentration in very low birth weight babies with posthemorrhagic ventricular dilatation. The association between measurements of lateral ventricle dilatation determined by serial ultrasound and brain specific creatine-kinase isoenzyme patterns (CK-BB) is studied in 60 very low birth weight preterm neonates of 1,500 g birth weight or 32 weeks gestation or less. The patients were divided into three groups according to cranial ultrasonographic findings: Group A (n = 20) had isolated peri-intraventricular hemorrhage (PIVH); group B (n = 20) had PIVH and dilated ventricles (VM); group C (n = 20) were normal matched preterms and formed the control group. Compared to control babies or those with isolated PIVH, high serum concentrations of CK-BB were observed after birth in babies with persistent dilated ventricles at two weeks postnatal age (p less than 0.01). No difference was found between CK-BB levels of babies with isolated PIVH and control group (p greater than 0.05). We suggest that an elevated CK-BB value is found in babies with persistent ventricular dilatation suggesting severe and diffuse brain damage after post-hemorrhagic ventriculomegaly (VM).


Relationship between benign epilepsy of children with centro-temporal EEG foci and febrile convulsions. In order to clarify the relationship between benign epilepsy of children with centro-temporal EEG foci (BECCT) and febrile convulsions (FC), we compared the previous and family histories of FC of one hundred children with BECCT, aged 3 years to 13 years, with those of 100 non-epileptic controls matched for age and sex. The incidences of FC in children with BECCT and non-epileptic controls were 18% and 8%, respectively (P less than 0.05). Forty-eight children (48%) with BECCT and 21 (21%) non-epileptic controls had positive family histories of FC within third-degree relatives (P less than 0.001). Of the fourteen pairs of siblings, one of each having BECCT and the other FC, we conducted an EEG examination in 7 siblings. All of these 7 siblings exhibited rolandic discharges (RD) on EEG. These observations strongly suggested a genetic link between BECCT and FC.


Squamous cell carcinoma of the lower lip. Most patients with squamous cell carcinoma of the lower lip present with early disease and follow a rather indolent clinical course. Determinant 5-year survival rates range from 85% to 95%. This study was undertaken in an attempt to gain insight into the cause of failure in those few patients who develop recurrent disease. A retrospective review was completed on patients treated between 1964 and 1990. Patients were staged according to the American Joint Committee. Patients with no palpable adenopathy had either a unilateral or bilateral suprahyoid dissection performed. Patients with palpable adenopathy underwent radical neck dissection. All patients were followed for evidence of recurrent disease. The records of 92 patients treated surgically for squamous cell carcinoma of the lower lip were available and complete. Palpable adenopathy was present in 38 patients; however, only 8 of these patients (21%) were histologically positive. Of the 54 patients judged to be free of disease, 3 (5.5%) had histologic evidence of metastasis. Overall, the incidence of cervical metastasis was 12%. The incidence of cervical metastasis in patients with squamous cell carcinoma of the lip is low; however, these data suggest that the size of the primary tumor does not correlate closely with predicting the incidence of regional lymph node metastases.


Electrophysiological study of four patients with Fisher syndrome: a mechanism of areflexia. Electrophysiological studies were performed on four patients with the Fisher syndrome (two 4-year-old boys, a 5-year-old boy and a 9-year-old girl). Motor nerve conduction velocity (MNCV), nerve action potential, F wave, H reflex and T reflex were measured at the stage when areflexia was present but ataxia and ophthalmoplegia had recovered. MNCV and SNCV by compound mixed nerve potential were normal in all our patients. The amplitude of the muscle responses (M-responses) and compound mixed nerve action potentials were also within normal limits. The latencies of the F waves and F wave conduction velocities were normal. However, H-reflexes and T-reflexes were absent in all four cases. Our results suggested that areflexia in the Fisher syndrome is attributed to the desynchronization of the impulses or the partial conduction block of GIa fibers.


Visuo-perceptual impairment and cerebral lesions in spastic diplegia with preterm birth. Eighteen cases of spastic diplegia (SD) ranging in age from 5 year 4 month to 9 year 5 month with preterm birth were studied to clarify the relationship between visuo-perceptual impairment and their cerebral lesions. All underwent neuropsychological examinations including the Frostig developmental test of visual perception, Tanaka-Binet or Suzuki-Binet intelligence test, and MRI examination. Cerebral lesions were detected in all subjects, and the volume of the peritrigonal white matter of the parietal and occipital lobes was significantly correlated with the visuo-perceptual impairment (r = 0.74, in the axial plane; r = 0.64, in the coronal plane). We propose that visuo-perceptual impairment is caused by cerebral lesions and that the measurement of peritrigonal white matter by MRI is useful for detecting potential visuo-perceptual impairment at an early age.


Tuberous sclerosis and Down syndrome: a casual association? This paper reports on the clinical, neurophysiological and neuroradiological characteristics of a patient with Down syndrome unusually associated with tuberous sclerosis. In particular, epilepsy is investigated in detail and its polygraphic study and etiopathological factors are discussed. The most interesting findings are those related to the presence of a structural abnormality of the rolandic-parietal cortex, bilaterally, in the form of pachygyria.


Vascular dysplasia in Down syndrome: a possible relationship to moyamoya disease. The brain of a child with Down syndrome (DS) and vascular abnormalities is described. Neuropathological examination showed a large cerebral infarction. In the circle of Willis there was hypoplasia of the left middle and posterior communicating cerebral arteries, and microscopically there was thickening of intima and focal disruption of internal elastica in some areas of the circle of Willis. Several reports suggest that the incidence of moyamoya disease is higher in children with DS than in other children. The high incidence of congenital heart disease in DS suggests an abnormality of vascular development that may manifest intracranially as a structural vascular defect, creating a vulnerability to unknown factors important in the pathogenesis of the moyamoya abnormality.


Ring 14 chromosome with complex partial seizures: a case report. A two-year-old girl was found to have a ring 14 chromosome: [46, XX, r(14) (P13 q32.3)]. Her development, including verbal ability, was retarded, her CT scan displayed a low density area anterior to the left temporal lobe, and she suffered from complex partial seizures. Focal central nervous system abnormalities may be present in patients with ring 14 chromosome, and their seizures are not exclusively of the primary generalized type. This is the first case with ring 14 chromosome and complex partial seizures.


Cortical reflex myoclonus associated with mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS): a case report. A 9-year-old female MELAS patient with myoclonus is reported, with emphasis on the results of electrophysiological studies of the myoclonus. At age 5 years she experienced a stroke-like episode, and a diagnosis of MELAS was made at age 6 years on the basis of muscle biopsy findings. At age 9 years spontaneous and segmental myoclonus, predominantly affecting the upper extremities, developed because of complications. Electrophysiological examination, including of somatosensory-evoked potentials (SEPs) and averaged EMG for long loop reflexes, revealed so-called "giant SEP" and enhanced long loop reflexes reflecting cortical hyperexicitability. Jerk-locked averaging yielded no myoclonus related spikes, but myoclonus-contingent 4-5 Hz theta bursts appeared. These findings suggest that some types of MELAS may be associated with cortical types of myoclonus.


Cerebral aneurysms in children.

Cerebral aneurysms in children. Childhood intracranial saccular aneurysms are rare, accounting for only 0.6-4.6% of all aneurysms. This paper presents two such cases. A 12-year-old boy developed sudden severe headaches. CT indicated subarachnoid hemorrhage in the bilateral sylvian fissure. Angiography failed to demonstrate any vascular lesions. Repeat angiography, however, revealed a 2 mm aneurysm on the right A-1. A miniclip was successfully applied to obliterate the aneurysm. The postoperative course was uneventful. In the second case, a 3-year-old boy, CT incidentally revealed a bullet-shaped high density area. Angiography demonstrated a large aneurysm arising from the insular portion of the prefrontal branch of middle cerebral artery. This large aneurysm with a broad-based neck was successfully clipped, employing the angioplastic and/or tandem clipping, despite the fact the prefrontal artery unfortunately was compromised in postoperative angiography. The patient was doing well postoperatively. Spontaneous subarachnoid hemorrhage (SAH) in childhood is uncommon. However, when children with SAH is encountered, angiography should be performed repeatedly even if the first angiogram does not demonstrate any vascular abnormality. Childhood aneurysms are increasingly being found incidentally in CT scans. The differences between child and adult aneurysms in regard to site, size, sex predominance, clinical features, and surgical outcome are discussed.


A case of Hallervorden-Spatz disease: progressive and intractable dystonia controlled by bilateral thalamotomy. We present a 10-year-old girl with Hallervorden-Spatz disease diagnosed clinically from the neurological manifestations and the characteristic MRI findings. Her main symptom, dystonia, was progressive and resistant to medication, but this dystonia was controlled by bilateral thalamotomy. No clinical progression of the symptoms was recognized at 21 months from the last operation.


A search for X-chromosome uniparental disomy and DNA rearrangements in the Rett syndrome. The cause of the Rett syndrome remains unknown but is thought to be related to X-chromosome abnormalities. Restriction fragment length polymorphism analysis was employed to search for X-chromosome DNA rearrangements and uniparental disomy in 16 probands and their families. Eighteen different probes, each specific for an area on either the long or the short arm of the X-chromosome, were used. DNA rearrangements were not detected at any of the tested loci. In addition, at each informative locus evidence of both maternal and paternal contributions was found in all probands. Thus, no evidence of either chromosomal abnormality or uniparental disomy was found in the population studied. If uniparental disomy is indeed a causative genetic mechanism for the Rett syndrome, its occurrence may only be infrequent.


Fetal alcohol syndrome: a case report of neuropsychological, MRI and EEG assessment of two children. Neuropsychological, neuroanatomical, and electrophysiological data are presented on two subjects with fetal alcohol syndrome (FAS). Both boys had intelligence quotients in the mentally deficient range and were found to have several other severe, specific deficits. Magnetic resonance imaging showed abnormalities of the corpus callosum, and reductions in the size of the basal ganglia and thalamic structures. No focal abnormalities were noted in the electroencephalogram records, although the electroencephalograms of both boys were moderately abnormal for their age group. A multidisciplinary approach to the study of FAS, hopefully will lead to a more unified concept of the disorder and perhaps indicate specific areas of vulnerability.


Chronic ethanol treatment induces H2O2 production selectively in pericentral regions of the liver lobule. Chronic treatment with ethanol damages pericentral regions of the liver selectively, and reactive oxygen species such as H2O2 may be involved in the mechanism of hepatotoxicity. To test this idea, the effect of chronic treatment with ethanol on rates of H2O2 production was measured in tissue cylinders isolated from periportal and pericentral regions of livers from ethanol-treated rats. Rates of hydrogen peroxide production, assessed from the oxidation of methanol to formaldehyde by catalase-H2O2, were similar in tissue cylinders isolated from periportal regions in control and ethanol-treated rats. In contrast, rates of H2O2 production were over 4-fold higher in tissue isolated from pericentral regions of livers from ethanol-treated than control animals (1.7 +/- 0.5 vs. 0.4 +/- 0.3 nmol/min/mg protein, respectively). Rates of H2O2-generating acyl CoA oxidase activity were equivalent in tissue cylinders from periportal regions of livers from both groups (approximately 2 nmol/min/mg protein), but were over 2-fold higher in tissue cylinders from pericentral regions of livers from ethanol-treated rats than from controls. In contrast, catalase activity was increased nearly 2-fold in homogenates from both periportal and pericentral regions by ethanol treatment while glutathione peroxidase activity was decreased significantly in both regions. These data demonstrate that ethanol increases H2O2 generation in pericentral regions of the liver lobule in part by elevating rates of peroxisomal beta-oxidation of acyl CoA compounds and are consistent with the hypothesis that local increases in H2O2 production may be involved in the mechanism of ethanol-induced hepatotoxicity.


Isolation and identification of phytoestrogens from beer. Two estrogenic substances of plant origin have been identified in beer using gas chromatography/mass spectrometry. These phytoestrogens, daidzein and genistein, have previously been shown to be biologically active in animals. Confirming the presence of biologically active phytoestrogens in beer and their possible presence in other beverages, suggests that there may be clinically significant effects related to sustained exposure to phytoestrogens contained in alcoholic beverages.


Modification of resistance to Streptococcus pneumoniae by dietary ethanol, immunization, and murine retroviral infection. Hallmarks of the acquired immune deficiency syndrome (AIDS) are immunologic alterations, frequently associated with opportunistic infections. To study such associations, LP-BM5 murine retrovirus infection was used as a murine model of AIDS. Retrovirally infected and uninfected mice were fed a 5% (v/v) ethanol diet for 55 days and then fed a 7% v/v ethanol diet for the final 7 days to assert the role of ethanol as a cofactor in development of murine AIDS. There was a reduction in polymorphonuclear neutrophils count in ethanol-fed groups. Neutrophils increased in retrovirus-infected groups, except those vaccinated 10 days before challenge with live bacteria. The percentage of splenic lymphocytes in the retrovirus-infected group was reduced in comparison with controls. Survival of the mice challenged intraperitoneally with Streptococcus pneumoniae was increased by vaccination and suppressed by dietary alcohol. Retrovirus infection caused a much faster death rate after bacterial challenge than nonretrovirus infected controls. Vaccination played an important role in delaying the death rate in all treated groups. Transferring spleen cells from healthy, unimmunized mice also enabled the retrovirally infected mice to survive the bacterial infection longer. Enhancement of resistance to S. pneumoniae by vaccination and transfer of immunocompetent cells to mice immunosuppressed by retroviral infection show the potential to use immunomodulation to affect disease resistance in AIDS.


Ethanol intake of chickens treated with fenfluramine, fluoxetine, and dietary tryptophan. Male, white leghorn chickens fed a standard diet with or without tryptophan supplementation were treated with single injections of 8 mg/kg fenfluramine in one series of experiments, or 8 mg/kg fluoxetine in another series. The birds had been food- and water-deprived prior to injection. They were offered, following the drug or saline injection, water, a 5% ethanol solution, or an isocaloric sucrose solution (8.75%) for 1 hr. Both fluoxetine and fenfluramine significantly reduced consumption of the ethanol solution, an effect exacerbated by tryptophan supplementation. Water or sucrose solution intake was also significantly reduced, but significantly less so than ethanol after fenfluramine injection. Since the birds drank significantly more of the sucrose solution after saline injection than of water, the consumption decrease caused by fenfluramine resulted, nevertheless, in a higher intake than that of either water or ethanol. Body temperature was decreased by ethanol intake and/or fluoxetine injection. Fenfluramine injection had an opposite, body temperature-increasing effect. It appears that both fenfluramine and fluoxetine decrease ethanol intake in a manner more specific than for water or sucrose, and that this effect is amplified by dietary tryptophan supplementation.


Surface exposure of synaptosomal gangliosides from long-sleep and short-sleep mice. A galactose oxidase/NaB[3H]4 technique was used to examine the relative surface exposure of gangliosides from whole brain synaptosomes of long-sleep (LS) and short-sleep (SS) mice. The surface exposure of the monosialoganglioside, GM1, did not differ between the two lines. Surface exposure of the polysialogangliosides GD1a, GD1b, and GT1b, however, was significantly greater in LS synaptosomes than in SS. Hydrolysis of the polysialogangliosides by neuraminidase to the end-product, GM1, at early time periods occurred more rapidly in LS than in SS synaptosomes. Upon exposure to either 250 mM or 50 mM ethanol, LS synaptosomal ganglioside surface exposure was decreased, but that of SS was increased. Pairwise comparisons of the individual ganglioside classes indicated that the decrease in LS synaptosomal ganglioside surface exposure was attributable to decreases in the polysialogangliosides, compared with controls. The ethanol-induced increase in SS synaptosomal ganglioside surface exposure, however, was mainly due to an increased surface exposure of only GD1a. These results suggest that intrinsic differences in the surface exposure of gangliosides and/or the magnitude and direction of ethanol-induced changes in ganglioside surface distribution may reflect biophysical or modulatory mechanisms by which this class of compounds modifies membrane sensitivity to ethanol. These results suggest that further studies should be performed to determine whether gangliosides are factors in genetically determined sensitivity to ethanol.


FTIR evidence for alcohol binding and dehydration in phospholipid and ganglioside micelles. We theorize that intoxicants and modern anesthetics bind at the membrane-water interface and displace (dehydrate) bound water molecules by breaking the hydrogen bonds. We tested this hypothesis by examining the effect of butanol on the binding of water to the polar regions of lipids in reversed micelles. Understanding the mechanisms of intoxication requires studies in physiologically relevant systems such as systems containing sialoglycoconjugates, especially gangliosides, which concentrate in the synapses of neural tissue. Therefore, we compared butanol effects on phospholipid with effects on ganglioside. Hydrogen-bond breaking activity of 1-butanol was studied in reversed micelles made of dipalmitoylphosphotidylcholine (DPPC), ganglioside (GM1 and GT1b) or the lipid mixture in a D2O-CCl4 medium. Fourier transform infrared spectroscopy (FTIR) data indicated that 1-butanol binds to DPPC and to gangliosides. Adding GM1 to the DPPC micelles introduces a new binding site for the alcohol. GT1b binds more butanol than GM1, because of more binding sites provided by extra sialic acid moieties. Spectral red shifts indicate that both water and butanol bind to the C = O group of sialic acid. Butanol partially releases the surface-bound water by disrupting hydrogen bonds, as indicated by an appearance of a sharp new free OD stretching band of the released D2O molecules. However, control studies with lipid-free systems in CCl4 revealed that a free OD peak could occur from a deuterium exchange reaction between D2O and 1-butanol(ol-h).(ABSTRACT TRUNCATED AT 250 WORDS)


Effect of calcitonin on the alcohol drinking of rats. Previous work has shown that calcitonin inhibits eating by rats and that it affects several neurotransmitter systems suspected to play a role in alcohol consumption. The present study was an initial test of whether calcitonin does affect voluntary alcohol consumption by male Wistar rats with prolonged alcohol experience. Calcitonin (20 IU/kg) or saline was injected subcutaneously on 10 consecutive days when the rats (n = 20) had continual access to 10% (v/v) ethanol solution, and to food and water. Using a cross-over design, the effects of 40 IU/kg calcitonin vs. saline were then examined in a second 10-day treatment period. Similar patterns of effects were obtained with both calcitonin doses, but the patterns differed with alcohol, food, and water intake. Alcohol drinking showed biphasic changes with both doses, producing highly significant Treatment x Day interactions (p < 1E-10 and p = 6E-7): it was significantly reduced on the first day of calcitonin treatment and significantly increased on the last few days. Food intake was reduced on all calcitonin days although most markedly on the first. Water drinking was not altered on the first calcitonin day, but was greatly increased on the second, then gradually returned toward the baseline. In a second experiment, the animals were switched to 1 hr of alcohol access per day, and calcitonin (20 IU/kg) was administered periodically to one group 4 hr before the alcohol access. Alcohol drinking was significantly reduced in all cases when the calcitonin injection was preceded by at least 1 day without calcitonin.(ABSTRACT TRUNCATED AT 250 WORDS)


Evidence for normal feedback inhibition of triiodothyronine on the thyrotropin (TSH) response to thyrotropin-releasing hormone (TRH) in abstinent male alcoholics. Disturbances in the hypothalamic-pituitary-thyroid (HPT) axis have been reported in abstinent, noncirrhotic alcoholics, including a reduction in thyrotropin (TSH) response to thyrotropin-releasing hormone (TRH) and reductions in triiodothyronine (T3). Some evidence has suggested that a portion of alcoholics may also exhibit a disturbance in the feedback inhibition of thyroid hormone on TSH release. To evaluate the function of the HPT axis negative feedback system in abstinent, noncirrhotic alcoholic men we compared the TSH response with TRH before and after a standard suppressive dose of T3. Ten alcoholic subjects were studied and compared with four control subjects from a previous study and to literature values. The mean percent reduction in TSH response in the alcoholic subjects of 74 +/- 7% was almost identical to the 71 +/- 9% reduction observed in normal subjects. The present findings indicate that noncirrhotic, abstinent alcoholic men exhibit normal suppression of the TSH response to TRH following T3.


The effects of maternal ethanol consumption on lactational transfer of immunity to Trichinella spiralis in rats. Transient immunity to the intestinal parasite Trichinella spiralis can be transferred from the mother to the neonate during lactation. The goal of this study was to determine whether maternal ingestion of ethanol during pregnancy and lactation inhibited expression of anti- T. spiralis immunity in nursing pups. Groups of female rats were infected with 1000 T. spiralis L1 larva, mated, and fed either ethanol-containing or isocaloric liquid diets and maintained on diets through pregnancy and lactation or were fed the liquid diets for 30 days before T. spiralis infection, mated, and maintained on diets through pregnancy and lactation. Pups were challenged orally with 200 T. spiralis larva at 14 days postdelivery (preweaning period) or 21 days postdelivery (postweaning period) and were sacrificed either 3 or 8 days after respective challenge. Intestinal worm counts and serum titers of anti-T. spiralis IgG antibodies were determined for each pup. No difference in the number of intestinal worms between pups of ethanol-treated and pair-fed dams that received ethanol diet after T. spiralis infection was observed in the preweaning period. This was also true of pups from the dams sacrificed at 3 days after challenge in the postweaning period. However, similar pups sacrificed at 8 days after challenge showed significantly higher worm counts (decreased immunity) relative to their pair-fed controls. Pups of dams that received ethanol containing diet 30 days prior to T. spiralis-infection showed significantly higher numbers of intestinal worms relative to pair-fed pups at both the preweaning and postweaning periods.(ABSTRACT TRUNCATED AT 250 WORDS)


Lactation and prolactin release in foster dams suckling prenatally ethanol exposed pups. The effect of prenatal ethanol exposure on lactation was studied employing prenatally ethanol-exposed pups transferred to foster dams following parturition. During pregnancy, from day 8 to term, dams consumed either standard laboratory chow (ad libitum control), or liquid diets containing 0%, 17.5%, or 35% ethanol derived calories (EDC). To equalize caloric intake, the 0% and 17.5% EDC groups were pair-fed to rats in 35% EDC group. Following delivery, pups born to dams fed with laboratory chow (control) or liquid diets containing 0, 17.5, or 35% EDC were adjusted to eight per litter and transferred to foster dams, which had been fed laboratory chow and water ad libitum throughout pregnancy. Foster dams were implanted with an atrial catheter on day 3 of lactation. On days 6 (early lactation) and 10 (midlactation), following separation of litters from dams for a 6-hr period, a baseline blood sample was removed via a catheter extension. Pups were weighed and returned to the dams. Subsequent blood samples were obtained 10, 30, 60, 120, and 180 min after initiation of suckling. Suckling latency and the amount of milk consumed during the 3-hr suckling were also determined. Litters were weighed on days 2, 6, 10, and 21. The prolactin surge in foster dams in response to suckling by prenatally ethanol-exposed pups was not altered on day 6 of lactation. On day 10, after the initial rise, suckling-induced prolactin was amplified in dams suckled by prenatally ethanol-exposed pups.(ABSTRACT TRUNCATED AT 250 WORDS)


Chronic ethanol and cocaine-induced hepatotoxicity: effects of vitamin E supplementation. The mechanisms of chronic cocaine toxicity and its potentiation by ethanol were investigated. Cocaine was administered to male C57BL/6 mice (20 mg/kg by peritoneal injection twice a day) alone or in combination with ethanol-containing diets (26% of total calories) supplied with a normal (20 IU/liter) or high content (170 IU/liter) of vitamin E. Liver levels of vitamin E, reduced glutathione, ascorbic acid, and hydroxyproline were measured. Accumulation of thiobarbituric acid-reactive substances, after in vitro stimulation of lipid peroxidation by Fe3+/ADP/ascorbate system, was measured as an index of susceptibility of hepatic membranes to oxidative stress. Plasma alanine aminotransferase, lethality, liver weight, and liver/body weight ratio were determined to assess the extent of liver toxicity. Consumption of ethanol exacerbated liver toxicity induced by cocaine treatments and reduced survival, but ethanol or cocaine treatments alone caused no or only modest mortality. Ethanol potentiated cocaine-induced accumulation of collagen in the liver and depletion of ascorbic acid. Hepatotoxicity induced by the combined ethanol plus cocaine treatment was not accompanied by a decrease in intracellular vitamin E or glutathione content. There were no changes in the basic levels and in the rate of accumulation of thiobarbituric acid-reactive substances in liver homogenates under the lipid peroxidation-stimulating system in vitro. The toxic effects of ethanol and cocaine were not reduced by the ingestion of vitamin E during short-term exposure of 21 days of treatment.


Enzymatic production of acetaldehyde from ethanol in rat brain tissue. The capacity for the brain to produce acetaldehyde (AcHO) from ethanol was determined in rat brain homogenates. Rat brains were perfused with saline-heparin solution and homogenized in a phosphate buffer. Varying amounts of tissue were incubated with ethanol (0-100 mM) for periods of up to 60 min. The reaction was stopped by the addition of desferrioxamine and ice-cold perchloric acid. Supernatants were treated with dinitrophenylhydrazine reagent, extracted with isooctane in the presence of an internal standard, and the derivatives were separated by HPLC. The addition of 4-methyl pyrazole (an alcohol dehydrogenase inhibitor) or metyrapone (a cytochrome P450 inhibitor) had no effect on the amount of recovered AcHO. On the other hand, treatment with the catalase inhibitors sodium azide, cyanamide, or 3-amino-1,2,4-triazole blocked the production of AcHO while the addition of exogenous peroxide or a peroxide-generating system enhanced the production of AcHO. Overall, these results suggest that AcHO may be produced in the brain during alcohol intoxication, through the action of the enzyme catalase.


Differences in hepatic microsomal cytochrome P-450 isoenzyme induction by pyrazole, chronic ethanol, 3-methylcholanthrene, and phenobarbital in high alcohol sensitivity (HAS) and low alcohol sensitivity (LAS) rats. High and low alcohol sensitivity (HAS and LAS) rats have been selected for their differences in ethanol-induced sleep time. Liver monooxygenase activities were studied in HAS and LAS rats before and after treatments with known inducers such as chronic ethanol, pyrazole, 3-methylcholanthrene (3-MC) and phenobarbital (PB) to determine whether the selection procedure also selected for differences in the cytochrome P-450 (P-450) inducibility. This previously has been shown with long sleep (LS) and short sleep (SS) mice, which were selected using a similar criterion. 3-MC and PB, in conjunction with chronic ethanol treatment, were used in order to evaluate the interactions of ethanol with these inducers. Prior to treatment, total P-450 content was slightly lower in LAS than in HAS rats. However, both lines displayed the same microsomal monooxygenase activities related to different P-450 isozymes. This was demonstrated by ethoxyresorufin deethylation (EROD) for cytochrome P-450 1A1 (CYP1A1), acetanilide hydroxylation (ACET) for CYP1A2, pentoxyresorufin dealkylation (PROD) for CYP2B, 1-butanol oxidation (BUTAN) and N-nitrosodimethylamine demethylation (NDMA) for CYP2E1. After the different treatments, HAS rats did not differ from LAS rats in their CYP2E1 inducibility. However, pyrazole, PB and 3-MC treatment led to differences in CYP1A and CYP2B monooxygenase activities between the two lines. The enhancement of PROD by pyrazole treatment was less prominent in LAS (1.7-fold of the control value) than in HAS rats (3.8-fold).(ABSTRACT TRUNCATED AT 250 WORDS)


A gastric alcohol dehydrogenase in the baboon: purification and properties of a 'high-Km' enzyme, consistent with a role in 'first pass' alcohol metabolism. The major isozyme of alcohol dehydrogenase in baboon stomach, ADH3, has been purified to homogeneity and characterized with a range of alcohol and aldehyde substrates. Using kcat/Km values as an indication of substrate efficacy, medium-chain length aliphatic alcohols and aldehydes were identified as the preferred substrates. ADH3 showed 'high-Km' properties with respect to ethanol, and is expected to significantly contribute to 'first-pass' metabolism of alcohol. The enzyme exhibited more than two orders of magnitude higher turnover of substrate than the baboon liver 'low-Km' ADH, and may play a role in the rapid metabolism of a wide range of ingested alcohols in the diet.


Alcohol-induced inhibition of LH secretion in intact and gonadectomized male and female rats: possible mechanisms. Alcohol (EtOH) is reported to decrease gonadotropin secretion, but the mechanisms mediating these changes are not fully understood. The present study examined the ability of acutely or chronically administered EtOH to alter plasma luteinizing hormone (LH) and follicle stimulating hormone (FSH) levels in both male and female rats, and correlated these changes with blood EtOH levels (BALs); investigated possible changes in the pituitary responsiveness of animals exposed to EtOH; and probed the role of the paraventricular nucleus (PVN) of the hypothalamus in mediating alcohol-induced decreases in plasma LH levels. The injection of 0.5 g EtOH/kg was accompanied by significantly higher BALs in females compared with males. This dose of alcohol did not alter rectal temperature, and only significantly (p < or = 0.01) decreased plasma LH levels in female rats. These findings were not altered by removal of gonadal steroids. Administration of 2.0 g EtOH/kg was followed by BALs that were comparable in both groups of rats at the 1- and 2-hr time-points, but were significantly (p < or = 0.01) higher in females 3 hr after treatment. Rectal T measurably decreased in all rats injected with 2 g EtOH/kg, though intact females showed the greatest change. This alcohol treatment also significantly (p < or = 0.01) inhibited immunoreactive LH release in both sexes, but there were no measurable changes in FSH values at any time.(ABSTRACT TRUNCATED AT 250 WORDS)


Chronic ethanol consumption induces accumulation of proteins in the liver Golgi apparatus and decreases galactosyltransferase activity. The effect of chronic ethanol consumption on labeled glycoprotein secretion and galactosyltransferase activity has been analyzed in cis- and trans-Golgi apparatus fractions isolated from rat liver. Rats were injected intraperitoneally with 3H-leucine, after different chase periods (30, 60, 180 min), and the radioactivity of the different subcellular fractions as well as of the isolated Golgi apparatus was measured. Chronic alcohol treatment induces an increase in liver weight as well as an enhancement of total liver protein. Ethanol treatment produces a significant accumulation of labeled proteins in isolated Golgi apparatus fractions after a 60- and 180-min chase. An accumulation of labeled proteins in the cytosolic fraction was observed only after 180 min. The alcohol treatment also induces a significant decrease in the activity of galactosyltransferase in both liver homogenate and Golgi apparatus fractions. These results suggest that an impairment of Golgi apparatus functions, including glycosylation and glycoprotein trafficking, could be one of the mechanisms involved in the accumulation of hepatic protein and thus in the pathogenesis of alcohol-induced injury in the liver of chronic ethanol-consuming animals.


Outcome in subjects with alcohol-provoked seizures. The outcome in 165 subjects with either an unknown (n = 93) or an alcohol-related (n = 72) seizure etiology, admitted to the emergency room of a general hospital in 1977-1978, was assessed after 10 years on the basis of subsequent hospital records and death-certificate-based mortality data. Alcohol and/or drug poisoning was the most frequent cause of death in the group with alcohol-related seizures. Sixty-four percent of the deaths in this group were directly related to alcohol abuse. The crude mortality was 45.8 (expected 8.6)/100 persons/10 years in the group with alcohol-related seizures and 15.1 (expected 6.0)/100 persons/10 years in the other group, the odds ratio between the groups being 4.8. Twenty percent of those with an unknown seizure etiology were found to show alcohol-related seizures, while the seizure etiology remained unknown in 59%, and a specific etiology other than alcohol abuse was revealed in 21% during the follow-up period. We conclude that alcohol abuse is an important, though often undetected, seizure etiology carrying a poor prognosis. The difference in mortality between the groups was due more to alcoholism than to seizures. There was no difference in mortality between those with a first alcohol-related seizure and those with previous alcohol-related seizures.


The Alcohol Clinical Index in lower socioeconomic alcohol-dependent men. The Alcohol Clinical Index, consisting of a 17-item Clinical Signs checklist and a 13-item Medical History questionnaire, was designed to provide an economic screening instrument for alcoholism not subject to self-report biases. There has been little validation work with this instrument. We therefore administered the Alcohol Clinical Index to a group of 40 alcohol-dependent men undergoing treatment at a VA Medical Center and a group of 17 nonalcoholic men being treated at an outpatient medical clinic at the same facility. The Clinical Signs checklist had high sensitivity, but poor specificity. Overall accuracy was 70% for a threshold score from 1 to 5. The Medical History questionnaire had more moderate sensitivity, but 100% specificity for a cutoff score of 2 or more. At a cutoff of 2, it had an overall accuracy of 84%. The high specificity of the Medical History questionnaire suggests that it could be used to help discriminate between alcoholics and nonalcoholics. Further study of these measures and individual items within the measures is recommended with different groups of alcohol users and nonusers.


Dose-ranging study of depot disulfiram in alcohol abusers. The object of this early Phase 2 study was to determine the dosage of depot disulfiram (DSF) required to induce sustained sensitivity to alcohol. Sixteen abstinent alcohol abusers were studied in an unblinded ascending-dose trial of DSF suspended in either (1) 5% methylcellulose or (2) 0.1% polysorbate 80. Five pairs of subjects received a single subcutaneous dose of Formulation A (1.0, 2.0, 2.5, 3.0, or 3.5 g). Three pairs were treated with Formulation B (60, 75, or 90 mg/kg) plus an oral loading dose of DSF (15 mg/kg). Subjects were challenged with oral alcohol (0.15 g/kg) before treatment, and on days 7, 14, 21, and 28. Subjective and objective responses to alcohol challenges (skin temperature, breath acetaldehyde, pulse rate, and blood pressure) were measured, and mobilization of DSF was assessed by carbon disulfide levels in breath. Treatment with Formulation B (75 or 90 mg/kg) plus an oral-loading dose (15 mg/kg) was consistently followed by sustained sensitivity to alcohol. Some subjects experienced the subjective and objective features of the DSF-ethanol reaction for 28 days, but these reactions achieved statistical significance only on day 7 for objective changes and on days 7 and 14 for subjective discomfort. Breath carbon disulfide was detectable until day 28 in all subjects receiving more than 1.0 g DSF, demonstrating sustained release of the drug. Treatment with depot DSF merits further study for its potential benefits in chronic alcohol abuse.


Ascites as a marker for the hyperdynamic heart of Laennec's cirrhosis. The purpose of this study was to determine the relation of the circulatory findings of cirrhosis to hepatic decompensation. Twenty individuals with biopsy-proven cirrhosis and 15 aged-matched controls underwent echocardiographic evaluation of cardiac function. Cardiac dimensions and indices derived from echocardiograms were related to various measures of liver decompensation. Cirrhotics had a higher heart rate, left ventricular end-diastolic volume, left ventricular ejection fraction, and cardiac output and a lower mean blood pressure and peripheral resistance than aged-matched subjects. On multiple regression analyses mean blood pressure, peripheral resistance, and cardiac output were all found to be related to estimates of ascites. Also, cirrhotics with ascites had a lower peripheral resistance than those without this finding. In clinically stable patients with cirrhosis, the presence of ascites indicates an intense vasodilatory state with a hyperdynamic circulation.


Relationship of insulin resistance to protein-energy malnutrition in patients with alcoholic liver cirrhosis: effect of short-term nutritional support. Protein-energy malnutrition (PEM) and insulin resistance (IR) are common features of alcoholic liver cirrhosis (ALC). In order to determine a relationship between them, nutritional status and glucose homeostasis were studied in 26 patients with ALC. Nutritional status was assessed through dietary, anthropometric, and biological parameters. An IR index (M/I) was obtained from the euglycemic insulin clamp technique. M/I was significantly correlated with accurate markers of PEM (albumin, transthyretin, and retinol-binding protein) but not with other markers of liver dysfunction. Nine patients were studied before and after nutritional support: M/I was significantly improved as were serum markers of PEM. Other markers of liver dysfunction were also significantly improved. These findings suggest that PEM could be responsible, in part, for IR in patients with ALC who are frequently malnourished. Moreover, nutritional support improved insulin sensitivity in these patients.


Brain morphologic characteristics of cirrhotic alcoholics and cirrhotic nonalcoholics: an MRI study. Cirrhotic alcoholics, cirrhotic nonalcoholics, and normal controls were compared on planimetric and subjective ratings of the MRI of the brain. The results indicated that the cirrhotic alcoholics exhibited more gross pathology than the nonalcoholic cirrhotics on ratings of frontal, parietal, and cerebellar atrophy; however, these groups were more similar to each other than they were different on planimetric measurements. The results are discussed in terms of the etiology and localization of the neuropathologic sequelae found commonly among alcoholics.


Oral magnesium supplementation improves metabolic variables and muscle strength in alcoholics. Magnesium deficiency is common among chronic alcoholics, but the knowledge of oral magnesium supplementation to this group is limited. We, therefore, randomized 49 chronic alcoholics, moderate to heavy drinkers for at least 10 years to receive oral magnesium or placebo treatment for 6 weeks according to a double-blind protocol. Effects on metabolic variables and muscle strength were analyzed. Significant reduction of aspartate-aminotransferase (ASAT), alanine-aminotransferase (ALAT) and gamma-glutamyl-transpeptidase (GGT) were seen after magnesium, whereas no change was observed with placebo. Bilirubin decreased in both groups. Serum Na, Ca, and P increased significantly during magnesium therapy compared with no statistically significant change in the placebo group. Serum K and Mg increased slightly after magnesium supplementation and decreased in the placebo group, resulting in a significant difference between the two groups at the end of the study. Muscle strength increased significantly during magnesium treatment, contrasting to no change with placebo. Blood pressure, heart rate, hematological variables, serum lipids (cholesterol, HDL, TG), glucose tolerance, and creatinine were unchanged in the two groups after treatment. Alcohol consumption was similar before and during the trial and does not explain the differences between the two groups The results shows that short-term oral magnesium therapy may improve liver cell function, electrolyte status, and muscle strength in chronic alcoholics.


Subjective feelings of alcohol intoxication in Asians with genetic variations of ALDH2 alleles. Asian-American men who possess ALDH2*2 alleles and who experience a facial flush after consuming alcohol were carefully matched on drinking history and demographic variables with nonflushing Asian males with only ALDH2*1 alleles. Each man was tested following placebo and a challenge dose of 0.75 ml/kg alcohol. Following alcohol, flushers reported experiencing significantly more positive feelings of intoxication than nonflushers, despite equivalent blood alcohol concentrations. These data suggest that Asians who flush after drinking, particularly those with ALDH2*1/2*2 genotype, have a more intense, although not necessarily a more negative, response to alcohol than comparable nonflushing Asians. This alcohol sensitivity reaction that many Asian flushers experience may contribute to their lower tendency to drink excessively, even though their response to alcohol is not predominantly negative.


The short-term psychological health of alcoholic and non-alcoholic liver transplant recipients. In response to limited resources and overwhelming clinical need, we previously developed an approach to alcoholic patient selection for liver transplant based on factors reported to predict short- and long-term sobriety in prospective studies of alcoholics. The present study reports follow-up data comparing alcohol dependent (n = 22, DSM-3-R criteria) and non-dependent (n = 39) subjects followed from 6 months to 3 years post-transplant. Nine percent of the alcoholics had returned to symptomatic drinking with 14% reporting some exposure to ethyl alcohol. Nearly half (46%) of the non-alcoholic group reported occasional social alcohol use. The alcoholic patients were less likely to be in their first marriage and more likely to be asked about alcohol use at follow-up clinic visits. In most other respects the two groups resembled each other more often than they differed. The alcoholic group reported continued high rates of prognostic factors associated with long-term abstinence although the content of these shifted noticeably between pre- and postoperative assessment. Members of both groups reported high frequencies of medication side effects, of missed doses of medications, and of depressive symptoms. Most felt the transplant had improved their lives but had brought on significant financial burden. There were no differences in subjective appraisals of either psychological or physical health between the two groups. These follow-up data suggest that carefully selected alcohol dependent patients will do as well as non-dependent patients after liver transplant.


Atopic eczema: role of microorganisms on the skin surface. The pathophysiology of atopic eczema (AE) is still poorly understood. One possible concept favors IgE-mediated reactivity towards allergens that enter the skin from the outside or through the blood. Microorganisms of the cutaneous flora also might represent a stimulus for allergic skin reactions. Abnormal bacterial skin colonization is a characteristic feature of AE. Staphylococcus aureus (S. aureus) is the most common pathogen. Binding to host cells involves special receptors, such as fibronectin or laminin. Specific IgE antibodies to S. aureus can be detected in the blood. Whereas the clinical relevance of anti-staphylococcal antibodies is still controversial, specific IgE antibodies to Pityrosporum species as well as positive type I prick test reactions to these yeasts seem to correlate with the intensity of eczematous lesions in the head and neck regions of patients with AE. Both antimicrobial and antifungal treatment has been shown helpful in some cases of AE.


Serum IgE levels and allergic spectra in immigrants to Sweden. We evaluated the allergy status of 134 immigrants from Asia, Africa, the Middle East and South America, who were referred to our clinic during the past 10 years. Fifty Swedish patients were used for comparison. When the atopy state was not taken into account, no significant difference was found between the two groups with respect to total IgE levels. However, IgE levels of non-atopic immigrants were significantly higher than the IgE levels of non-atopic Swedes. While there was no significant difference in IgE levels between atopic and non-atopic immigrants, this difference was significant in Swedish patients. In general, IgE levels of immigrants showed a decline with time and reached approximately the same levels as for the Swedish patients in 10.5 years. In the immigrant group atopic women had a considerably lower IgE level than the atopic men. Among the atopics there were no differences between sexes. In Swedes and immigrants pollen was the most common group of allergens. The spectrum of allergy in the immigrant group changed with time in Sweden, and gradually became more similar to the Swedish spectrum. Skin and/or RAST positivity to birch increased from 16% within 2.5 years to 53% after more than 10.5 years in Sweden. Our data indicate that environmental factors rather than hereditary differences determine the IgE state. Within a few years the immunologic status of immigrants adapts to the new environment.


Clinical and immunological effects of immunotherapy with alum-absorbed grass allergoid in grass-pollen-induced hay fever. A double-blind, placebo-controlled study of immunotherapy was conducted in 19 patients with grass-pollen hay fever to evaluate the efficacy and safety of a formalinized depot grass allergoid. The patients were assessed before and during IT by clinical (symptom-medication scores during the grass- pollen season, specific nasal and skin reactivity) and immunological (specific IgE, IgG, IgG1 and IgG4 antibodies) parameters. High doses of grass allergoid, corresponding to a cumulative pre-seasonal dosage of 46,050 PNU, were administered, with only one systemic reaction. The actively treated patients had significantly lower symptom-medication scores than placebo (p less than 0.01) during the month of May and showed a significant decrease in specific skin (p less than 0.01) and nasal (p less than 0.05) reactivity, and a significant early increase in specific IgE (p less than 0.01), IgG (p less than 0.0005), IgG1 (p less than 0.001) and IgG4 (p less than 0.05), with a subsequent decrease of IgE and IgG1. No differences were detected in any of these parameters in the placebo group. A correlation was found between high IgG4/IgG1 ratio and the specific skin reactivity decrease (r = 0.691, p less than 0.05), whereas a high IgG4/IgG1 ratio was associated with higher symptom-medication scores (r = 0.654, p less than 0.05). Possible explanations of these apparent discrepancies are proposed.


Is atopy a risk factor for the use of contact lenses? We studied the tolerance of soft contact lenses (CL) in 24 atopic (16 with hay fever) and 52 non-atopic subjects with a mean age of 20 years. They were examined when they first came to an ophthalmologist to have CL and re-examined after an average of 1.7 years. All subjects were allowed to use CL throughout the year, including the pollen season. Of the 76 subjects, 31 (41%) reported some kind of eye symptoms during the use of CL. Six subjects (8%) had stopped using CL because of symptoms. Altogether, in 29/76 subjects (38%) some objective sign was detected in the examination, confirming the subjective symptoms (conjunctivitis 16, keratoconjunctivitis 8, increased limbal blood vessels 4, and eczema palpebrae 1). Fourteen of the 24 atopics (58%) had experienced symptoms compared with 17 of the 52 non-atopics (33%) (p = 0.034). Eleven atopics had seasonal eye symptoms, and eight of them (73%) had problems with CL use. Eosinophils and neutrophils found in the conjunctival scrapings at the first examination appeared to predict poor CL tolerance when the occurrence of symptoms in different groups was first compared by bivariate analysis. The risk factors that could predict poor CL tolerance were also evaluated, with logistic regression analysis controlling potential confounders. History of an atopic condition increased 5-fold the risk of experiencing various external eye symptoms during the use of CL. We conclude that seasonal atopic allergy is a especially risk factor for wearing soft contact lenses, and their use should be restricted during the season.


Specific IgE antibodies to vespids in the course of immunotherapy with Vespula germanica administered to patients sensitized to Polistes dominulus. Sera from a group of 12 patients with anaphylactic reactions to vespids were studied. Field observations and RAST values suggested that the offending insect was Polistes dominulus (PD). Specific IgE antibodies to PD appeared in all cases and to Vespula germanica (VG) in nine. Absorption studies in these basal sera showed that IgE antibodies to VG were due to cross-reactivity with PD. The RAST value to both venoms was higher after immunotherapy (IT) in six cases. IgE antibodies increased to determinants common to both vespids, and in 41% of the cases to specific epitopes of VG venom allergens not initially detected in the basal sera. In one case antibodies increased only to VG without a corresponding rise to PD. These results indicate that if the correct venom to which the individuals are sensitized is not administered IgE antibodies may appear which were not initially detected in the patients' sera. The levels of these antibodies declined during the course of IT.


Circulatory basophilia in guinea pigs with delayed-type hypersensitivity. Topical antigenic provocation induces circulatory basophilia. Circulatory basophilia could be induced in inbred guinea pigs systematically immunized with ovalbumin and consequently provoked repeatedly with dissolved ovalbumin applied onto the mucosa of the nares or the outer eye. The degree of the increase in circulatory basophil granulocytes depended on the adjuvant used and was significantly more pronounced after immunization with Freund's complete adjuvant than with alhydrogel (Al(OH)3). The degree of basophilia was also dependent on the animal strain, but different in two strains selected for high-asthma trait.


Protective effect of different doses of terfenadine on the conjunctival provocation test. The protective effect of terfenadine on inflammatory processes following the early phase of conjunctival provocation tests by specific allergen was assessed in 24 patients suffering from seasonal allergic rhinoconjunctivitis, in a single-blind, randomized, placebo-controlled, parallel-group study. Patients were randomly assigned to four treatment groups, each being given terfenadine 60, 120, 180 mg daily, or placebo, respectively, for 7 days, out of the pollen season. Clinical severity (burning, itching, lacrimation and hyperemia), and number of inflammatory cells obtained by conjunctival scraping (neutrophils, eosinophils, lymphocytes, and monocytes) were evaluated before and after treatment. Pre-treatment with terfenadine resulted in a significantly higher allergen threshold dose than placebo (p less than 0.01), regardless of drug dose. Patients given terfenadine experienced a significant reduction (p less than 0.03) in conjunctival symptom severity, as compared with placebo, following conjunctival challenge. Accordingly, the number of inflammatory cells in terfenadine-treated patients was significantly lower (p less than 0.01) than in the placebo-treated after the conjunctival provocation test. The results of this study suggest that terfenadine has a significant protective effect on the early-phase cellular and clinical events of conjunctival reaction induced by allergen challenge in atopic patients.


A double-blind comparison of nasal budesonide and oral astemizole for the treatment of perennial rhinitis. Sixty-nine outpatients with symptomatic perennial rhinitis were recruited to this double-blind, parallel-group study to compare budesonide nasal spray with oral astemizole. Following a 1-week run-in on placebo, 67 patients achieved a mean daily total symptom score of at least 4 (scoring for each symptom was 0 = none, 1 = mild, 2 = moderate, 3 = severe), and were randomized to study treatments - 33 to budesonide, 100 micrograms in each nostril morning and evening, and 34 to astemizole, one 10-mg tablet each morning, for a period of 4 weeks. No antihistamine preparations other than eye drops and no corticosteroids were permitted during the active treatment period. Patients recorded symptoms of blocked nose, runny nose, sneezing, itchy nose, sore eyes or runny eyes in diary cards each evening before retiring. Diary card data showed that there was significantly greater improvement in blocked nose, runny nose and runny eyes during the first 2 weeks of budesonide treatment than during the same period on astemizole. A similar, although non-significant, trend was observed for sneezing and itchy nose, but there was no apparent difference in the reporting of sore eyes. After 4 weeks, blocked nose and runny nose remained significantly less troublesome in the budesonide group. Both treatments were well-tolerated and no major adverse effects were reported. Patient ratings for treatment efficacy were significantly higher for budesonide than astemizole at both 2 weeks and 4 weeks.


Local nasal immunotherapy in allergic rhinitis to Parietaria. A double-blind controlled study. Preseasonal local nasal immunotherapy (LNIT) by means of an extract in macronized powder form has been studied in allergic rhinitis to parietaria. Twenty-four Parietaria-sensitive patients have been studied for 18 weeks in a double-blind controlled trial. Subjects were selected on the basis of a positive skin test, RAST and intranasal challenge to Parietaria antigen. Three eight-patient groups were randomly planned: the first group was given native Parietaria product, the second modified Parietaria product, and the third placebo. During the pollen season no difference was observed in mean weekly symptom score between the three groups, while the mean weekly medication score was significantly lower in the treated groups than the control group. Only the treated groups showed a significant increase in specific nasal threshold to Parietaria after treatment. Adverse reactions to LNIT, limited to the upper respiratory tract, occurred rarely and did not interfere with the dose schedule. This study indicates that LNIT in powder form may be a suitable alternative to the traditional subcutaneous immunotherapy in terms of clinical efficacy and safety.