Predicting reamputation risk in patients undergoing lower extremity amputation due to the complications of peripheral artery disease and/or diabetes.

BACKGROUND: Patients undergoing amputation of the lower extremity for the complications of peripheral artery disease and/or diabetes are at risk of treatment failure and the need for reamputation at a higher level. The aim of this study was to develop a patient-specific reamputation risk prediction model. METHODS: Patients with incident unilateral transmetatarsal, transtibial or transfemoral amputation between 2004 and 2014 secondary to diabetes and/or peripheral artery disease, and who survived 12 months after amputation, were identified using Veterans Health Administration databases. Procedure codes and natural language processing were used to define subsequent ipsilateral reamputation at the same or higher level. Stepdown logistic regression was used to develop the prediction model. It was then evaluated for calibration and discrimination by evaluating the goodness of fit, area under the receiver operating characteristic curve (AUC) and discrimination slope. RESULTS: Some 5260 patients were identified, of whom 1283 (24·4 per cent) underwent ipsilateral reamputation in the 12 months after initial amputation. Crude reamputation risks were 40·3, 25·9 and 9·7 per cent in the transmetatarsal, transtibial and transfemoral groups respectively. The final prediction model included 11 predictors (amputation level, sex, smoking, alcohol, rest pain, use of outpatient anticoagulants, diabetes, chronic obstructive pulmonary disease, white blood cell count, kidney failure and previous revascularization), along with four interaction terms. Evaluation of the prediction characteristics indicated good model calibration with goodness-of-fit testing, good discrimination (AUC 0·72) and a discrimination slope of 11·2 per cent. CONCLUSION: A prediction model was developed to calculate individual risk of primary healing failure and the need for reamputation surgery at each amputation level. This model may assist clinical decision-making regarding amputation-level selection.

Circadian clock resetting by behavioral arousal: neural correlates in the midbrain raphe nuclei and locus coeruleus.

Some procedures for stimulating arousal in the usual daily rest period (e.g., gentle handling, novel wheel-induced running) can phase shift circadian rhythms in Syrian hamsters, while other arousal procedures are ineffective (inescapable stress, caffeine, modafinil). The dorsal and median raphe nuclei (DRN, MnR) have been implicated in clock resetting by arousal and, in rats and mice, exhibit strong regionally specific responses to inescapable stress and anxiogenic drugs. To examine a possible role for the midbrain raphe nuclei in the differential effects of arousal procedures on circadian rhythms, hamsters were aroused for 3 h in the mid-rest period by confinement to a novel running wheel, gentle handling (with minimal activity) or physical restraint (with intermittent, loud compressed air stimulation) and sacrificed immediately thereafter. Regional expression of c-fos and tryptophan hydroxylase (TrpOH) were quantified immunocytochemically in the DRN, MnR and locus coeruleus (LC). Neither gentle handling nor wheel running had a large impact on c-fos expression in these areas, although the manipulations were associated with a small increase in c-Fos in TrpOH-like and TrpOH-negative cells, respectively, in the caudal interfascicular DRN region. By contrast, restraint stress significantly increased c-Fos in both TrpOH-like and TrpOH-negative cells in the rostral DRN and LC. c-Fos-positive cells in the DRN did not express tyrosine hydroxylase. These results reveal regionally specific monoaminergic correlates of arousal-induced circadian clock resetting, and suggest a hypothesis that strong activation of some DRN and LC neurons by inescapable stress may oppose clock resetting in response to arousal during the daily sleep period. More generally, these results complement evidence from other rodent species for functional topographic organization of the DRN.

Robust food anticipatory circadian rhythms in rats with complete ablation of the thalamic paraventricular nucleus.

Rats can anticipate a fixed daily mealtime by entrainment of a circadian timekeeping mechanism anatomically separate from the light-entrainable circadian pacemaker located in the suprachiasmatic nucleus. Neural substrates of this food-entrainable circadian system have not yet been fully elucidated. A role for the thalamic paraventricular nucleus (PVT) is suggested by observations that scheduled feeding synchronizes daily rhythms of glucose utilization and immediate early gene and circadian clock gene expression in this area. One study has reported absence of food anticipatory circadian activity rhythms in rats with PVT ablations. To determine whether this effect extends to other behavioral measures of food anticipation, rats received large radiofrequency lesions aimed at the PVT and were maintained on a 3-h meal provided each day 6 h after lights-on. Rats with unambiguously complete PVT ablation exhibited increased total daily activity, a change in the waveform of the nocturnal activity rhythm, but no change in the amplitude, duration, latency to appearance or persistence during total food deprivation of food anticipatory activity measured by activity at or near a food bin accessible via a small window in the recording cage. These results indicate that, while the PVT may modulate light-entrainable rhythms, it is not a critical input, oscillator or output component of the circadian system by which rats behaviorally anticipate a daily mealtime.

Persistence of a behavioral food-anticipatory circadian rhythm following dorsomedial hypothalamic ablation in rats.

Circadian rhythms of behavior in rodents are regulated by a system of circadian oscillators, including a master light-entrainable pacemaker in the suprachiasmatic nucleus that mediates synchrony to the day-night cycle, and food-entrainable oscillators located elsewhere that generate rhythms of food-anticipatory activity (FAA) synchronized to daily feeding schedules. Despite progress in elucidating neural and molecular mechanisms of circadian oscillators, localization of food-entrainable oscillators driving FAA remains an enduring problem. Recent evidence suggests that the dorsomedial hypothalamic nucleus (DMH) may function as a final common output for behavioral rhythms and may be critical for the expression of FAA (Gooley JJ, Schomer A, and Saper CB. Nat Neurosci 9: 398-407, 2006). To determine whether the reported loss of FAA by DMH lesions is specific to one behavioral measure or generalizes to other measures, rats received large radiofrequency lesions aimed at the DMH and were recorded in cages with movement sensors. Total and partial DMH ablation was associated with a significant attenuation of light-dark-entrained activity rhythms during ad libitum food access, because of a selective reduction in nocturnal activity. When food was restricted to a single 3-h daily meal in the middle of the lights-on period, all DMH and intact rats exhibited significant FAA. The rhythm of FAA persisted during a 48-h food deprivation test and reappeared during a 72-h deprivation test after ad libitum food access. The DMH is not the site of oscillators or entrainment pathways necessary for all manifestations of FAA, but may participate on the output side of this circadian function.

Functional outcome after open repair of abdominal aortic aneurysm.

INTRODUCTION: Detailed information on functional outcome after open abdominal aortic aneurysm (AAA) repair is sparse. Information about functional outcome of open AAA repair is essential to allow comparison of treatment modalities. METHODS: To determine the functional outcome of patients after open repair of AAA, we reviewed 154 consecutive, nonemergency open repairs of infrarenal AAAs between 1990 and 1997 and each patient's medical records. Clinical variables were recorded for each patient, as were multiple outcomes, including ambulatory status, independent living status, current medical condition, and the patient's perception of recovery and satisfaction. Eighty-seven patients or their families were available for current telephone interview to obtain information about objective functional activities, including walking and driving, and subjective functional information, including assessment of complete recovery and willingness to undergo AAA repair again. Chart data were available for all 154 patients. RESULTS: There were 42 women and 112 men. A total of 139 operations were elective, and 15 were urgent. The operative mortality rate was 4%, mean hospital stay was 10.7 +/- 1.3 days, and mean intensive care unit stay was 4.57 +/- 1.17 days. Seventeen (11%) patients required transfer to a skilled nursing facility with a mean stay of 3.66 +/- 2.9 months. All patients were ambulatory preoperatively, whereas at last follow-up (median, 25 months; range, 0.13-108.5 months), 100 (64%) of the patients remained ambulatory, 34 (22%) required assistance, and 12 (14%) were nonambulatory. At current assessment by telephone interview, 33% of patients described a decrease in their functional activity including driving, shopping, and traveling compared with their preoperative status, whereas 67% were unchanged. When asked to assess their own degree of recovery, 64% of patients stated that they experienced complete recovery with an average time to recovery of 3.9 months, whereas 33% said they had not fully recovered at a mean follow-up of 34 months. Sixteen (18%) patients said they would not undergo AAA repair again knowing the recovery process, even though they appeared to fully understand the implication of AAA rupture. CONCLUSION: Patients undergoing open AAA repair generally experienced significant freedom from surgical complications. However, substantial functional impairment was present. It is unclear whether the functional disability resulted from the AAA surgery or from aging and comorbidities unrelated to surgery.

Relationship between antiphospholipid antibodies and progression of lower extremity arterial occlusive disease after lower extremity bypass operations.

PURPOSE: Antiphospholipid antibodies (APLs), which consist of anticardiolipin antibodies (ACLs) or lupus anticoagulant (LA), are associated with venous thrombosis, stroke, and cardiac events. Although they are present in many patients with lower extremity atherosclerotic occlusive disease (LEAOD), the relationship between APL and the progression of LEAOD has not been reported. A comparison of progression of LEAOD as determined with direct imaging studies in patients with and without APL forms the basis for this report. METHODS: APL+ patients (immunoglobulin M [IgM] or IgA or IgG ACL > 3 SD units above control mean or positive LA) who underwent lower extremity bypass grafting between January 1990 and June 1999 (n = 79) were compared with an APL control group (n = 68). Members of the study and control groups were similar with respect to age, procedure, sex, length of follow-up, and multiple atherosclerosis risk factors. Progression of LEAOD was determined by comparing preoperative arteriograms with postoperative imaging studies (arteriograms or duplex scanning). External iliac, common femoral, superficial femoral and popliteal arteries were graded as < 50% stenosis, > or = 50% stenosis, or occluded. Posterior tibial and anterior tibial arteries were graded as patent or occluded. Progression was defined as any increase in stenosis category. RESULTS: The mean follow-up period was 31 months for APL+ and 35 months for APL- patients (P = not significant). Progression of LEAOD occurred in 58 (73%) of 79 APL+ patients and in 25 (37%) of 68 APL- patients (P <.001). There was no difference in progression in external iliac or common femoral arteries. Differences in progression were noted in more distal arteries; APL+ patients had significantly more progression in superficial femoral (45% vs 16%, P <.01), popliteal (31% vs 12%, P <.01), posterior tibial (29% vs 13%, P <.05), and anterior tibial arteries (29% vs 14%, P <.05). Multivariate logistic regression analysis showed a significant independent association between the presence of APL and progression of LEAOD (P <.0001). CONCLUSION: In this study, the presence of APL in patients undergoing lower extremity bypass operations was a significant independent risk factor for progression of LEAOD. We conclude that this patient group should be closely monitored in the postoperative period and appears ideally suited for prospective studies of therapies to modify LEAOD progression.

Long-term functional outcome of neurogenic thoracic outlet syndrome in surgically and conservatively treated patients.

PURPOSE: Neurogenic thoracic outlet syndrome (NTOS) in the absence of bony and electrodiagnostic abnormalities, often referred to as disputed NTOS, remains enigmatic. Optimal treatment, especially the role of surgery, is controversial. The long-term functional outcome of a cohort of patients undergoing independent medical examination for disputed NTOS with symptoms sufficiently severe to cause inability to work forms the basis for this report. METHODS: Patients with disputed NTOS and symptoms sufficiently severe to cause at least temporary inability to work seen for independent medical examinations from 1990-1998 formed the study group. None of the patients were treated by our group. Functional outcome was assessed with information from a standardized telephone interview or patient questionnaire. The patients' ability to return to work and an assessment of their current level of symptoms and symptom progression since the time of onset were determined. RESULTS: Seventy-nine patients were reevaluated at a mean follow-up of 4.2 years (range, 2-7.5 years) after our initial evaluation. Fifteen patients (19%) underwent first rib resection surgery performed by others, whereas 64 (81%) had no surgery. Patients undergoing surgery had missed more work time than those undergoing conservative management (27.6 +/- 6.0 months vs 14.9 +/- 2.6 months, P <.04). Return to work was achieved in nine patients who were operated on (60%) and in 50 patients who were not operated on (78%) (P = not significant [NS]). Among operated patients, current assessment of symptom severity was severe, moderate, mild, and asymptomatic in 7%, 47%, 40% and 7%, respectively. This distribution did not differ significantly from that observed in nonoperated patients (11%, 55%, 30%, 5%; P = NS). When asked about changes in symptomatic status since onset, 7% of the operated group had complete resolution, 27% had marked improvement, 40% had minimal improvement, 13% had no improvement, and 13% were worse. This did not differ significantly from the change in symptoms reported by the nonoperated group (2%, 30%, 22%, 31%, 16%; P = NS). CONCLUSION: Most patients with disputed NTOS in this nonrandomized series were able to return to work and demonstrated an improvement of symptoms with long-term follow-up. First rib resection did not improve functional outcome in this group.

Optimizing duplex follow-up in patients with an asymptomatic internal carotid artery stenosis of less than 60%.

OBJECTIVES: The Asymptomatic Carotid Atherosclerosis Study established benefit of carotid endarterectomy for 60% to 99% asymptomatic internal carotid artery (ICA) stenosis. Optimal follow-up intervals to detect progression from < 60% to 60%-99% ICA stenosis are unknown. In a previous study from our laboratory, we found that ICAs with < 60% stenosis and peak systolic velocities (PSVs) of 175 cm/s or more on initial duplex were at high risk for progression. Prospective evaluation of this hypothesis and determination of optimal duplex follow-up intervals for asymptomatic patients with < 60% ICA stenosis form the basis of this report. METHODS: All patients who underwent initial carotid duplex examination for any indication since January 1, 1995, with at least one patent, asymptomatic, previously nonoperated ICA with < 60% stenosis; with 6 months' or greater follow-up; and with one or more repeat duplex examinations were entered into the study. On the basis of the initial duplex examination, ICAs were classified into two groups: those with a PSV less than 175 cm/s and those with a PSV of 175 cm/s or more. Follow-up duplex examinations were performed at varying intervals to detect progression from < 60% to 60%-99% ICA stenosis with criteria previously reported (both PSV > or = 260 cm/s and end-diastolic velocity > or = 70 cm/s). RESULTS: A total of 407 patients (640 asymptomatic ICAs with < 60% stenosis) underwent serial duplex scans (mean follow-up, 22 months). Three ICAs (0.5%) became symptomatic and progressed to 60%-99% ICA stenosis at a mean of 21 months (all transient ischemic attacks), whereas four other ICAs occluded without stroke during follow-up. Progression to 60%-99% stenosis without symptoms was detected in 46 ICAs (7%) (mean, 18 months). Of the 633 patent asymptomatic arteries, 548 ICAs (87%) had initial PSVs less than 175 cm/s, and 85 ICAs (13%) had initial PSVs of 175 cm/s or more. Asymptomatic progression to 60%-99% ICA stenosis occurred in 22 (26%) of 85 ICAs with initial PSVs of 175 cm/s or more, whereas 24 (4%) of 548 ICAs with initial PSVs less than 175 cm/s progressed (P <.0001). The Kaplan-Meier method was used to determine freedom from progression at 6 months, 12 months, and 24 months, which was 95%, 83%, and 70% for ICAs with initial PSVs of 175 cm/s or more versus 100%, 99%, and 95%, respectively, for ICAs with initial PSVs less than 175 cm/s (P <.0001). CONCLUSIONS: Patients with < 60% ICA stenosis and PSVs of 175 cm/s or more on initial duplex examination are significantly more likely to progress asymptomatically to 60%-99% ICA stenosis, and progression is sufficiently frequent to warrant follow-up duplex studies at 6-month intervals. Patients with < 60% ICA stenosis and initial PSVs less than 175 cm/s may have follow-up duplex examinations safely deferred for 2 years.

Patency and characteristics of lower extremity vein grafts requiring multiple revisions.

OBJECTIVES: Multiple (> 1) revisions of lower extremity vein grafts may be required to maintain patency. Characteristics of recurrent lower extremity vein graft lesions and the patency achieved after multiple revisions have not been emphasized in reports on infrainguinal vein graft stenosis. This study was performed to determine (1) the patency of multiply revised lower extremity vein grafts and (2) the timing, location, and angiographic and duplex features of the recurrent lesions. METHODS: Lower extremity vein grafts that were followed in a duplex surveillance protocol and required revisions from January 1990 through December 1998 were identified. All revisions were preceded by angiography. In multiply revised lower extremity vein grafts, the immediate preoperative angiogram and duplex examination findings, as well as the angiogram made before the previous revision and the duplex study done after the previous revision, were reviewed to characterize recurrent lesions at the time of previous and current graft revision. The patencies of grafts undergoing single and multiple revisions were compared. RESULTS: A total of 233 lower extremity vein graft revisions were performed; of these, 50 (21%) were repeat revisions. Of grafts requiring more than one revision, 98% were normal on duplex examination after the initial revision. Five-year assisted primary patency of multiply revised grafts (91%) was not different from that of grafts with a single revision (89%; P not significant). Of 60 lesions repaired in the 50 repeat revisions, 29 (48%) were at the previously revised site, and 31 (52%) were at new sites. The time between revisions was less if the same site was revised (11 +/- 2 months) than if a different site required revision (20 +/- 4 months; P <.05). Arteriographic evidence of a minor (< 50% diameter) lesion was present at the time of the initial revision in 23% of cases in which revision of a second site was subsequently required. CONCLUSION: In our experience, 21% of lower extremity vein grafts requiring initial revision ultimately require additional revisions. Multiply revised lower extremity vein grafts have excellent long-term patency. Lesions occur with equal frequency at the site of prior revision and new sites. Lesions prompting revision at new sites occur significantly later and are infrequently detected on prior imaging studies.

Raynaud's syndrome in workers who use vibrating pneumatic air knives.

PURPOSE: The use of vibrating tools has been shown to cause Raynaud's syndrome (RS) in a variety of workers, including those who use chain saws, chippers, and grinders. The diagnosis of RS in workers who use vibrating tools is difficult to document objectively. We studied a patient cohort with RS caused by the use of a vibrating pneumatic air knife (PAK) for removal of automobile windshields and determined our ability to document RS in these workers by means of digital hypothermic challenge testing (DHCT), a vascular laboratory study that evaluates digital blood pressure response to cooling. METHODS: Sixteen male autoglass workers (mean age, 36 years) with RS were examined by means of history, physical examination, arm blood pressures, digital photoplethysmography, screening serologic studies for underlying connective tissue disorder, and DHCT. RESULTS: No patient had RS before they used a PAK. The mean onset of RS (color changes, 100%; pain, 93%; parathesias, 75%) with cold exposure was 3 years (range, 1.5 to 5 years) after initial PAK use (mean estimated PAK use, 2450 hours). Fifty-six percent of workers smoked cigarettes. The findings of the physical examination, arm blood pressures, digital photoplethysmography, and serologic testing were normal in all patients. At 10 degrees C cooling with digital cuff and patient cooling blanket, a significant decrease in digital blood pressure was shown by means of DHCT in 100% of test fingers versus normothermic control fingers (mean decrease, 75%; range, 25% to 100%; normal response, less than 17%; P <.001). The mean follow-up period was 18 months (range, 1 to 47 months). No patient continued to use the PAK, but symptoms of RS were unchanged in 69% and worse in 31%. CONCLUSION: PAK use is a possible cause of vibration-induced RS. The presence of RS in workers who use the PAK was objectively confirmed by means of DHCT. Cessation of PAK use in the short term did not result in symptomatic improvement.

Duplex scanning alone is not sufficient imaging before secondary procedures after lower extremity reversed vein bypass graft.

PURPOSE: Duplex surveillance of lower extremity reversed vein bypass grafts (LERVG) is a means of identifying patients at risk for occlusion. The perceived accuracy of duplex scan as a means of identifying stenoses has led many surgeons to perform graft revision on the basis of duplex scan alone. This may result in missing additional lesions that are threatening patency. To assess the role of duplex scan as the sole imaging method before revision of LERVGs, we reviewed consecutive patients undergoing revisions who underwent preoperative arteriography after identification of duplex scan abnormalities. METHODS: Duplex scan results, operative reports, and preoperative arteriograms for patients undergoing LERVG revision from January 1990 to December 1997 were reviewed. A standard duplex scan surveillance protocol was followed, and attempts were made to survey the entire graft, including inflow and outflow. Duplex scan results were compared with the results of preoperative arteriograms and the operation performed to determine if all significant lesions were identified by means of duplex scan alone. RESULTS: Two hundred five LERVG revisions were performed. The 5-year assisted primary patency rate was 91%. In 119 cases (58%), arteriography did not contribute significantly to duplex scan findings. Arteriography significantly contributed to operative planning in 86 cases (42%). In 38 cases (19%), only a low-flow state was identified by means of duplex scan, and a correctable stenosis was identified by means of arteriography. In 48 cases (23%), additional significant lesions corrected at operation were identified by means of arteriography. These included 26 inflow, 16 graft, and 8 outflow lesions. Arteriography was most useful as a means of determining the revision procedure performed when there were inflow lesions (P <.05) or when the proximal anastomosis was to the profunda or superficial femoral arteries (P <.05). All frequently performed bypass graft configurations had some discrepancy between arteriographic and duplex scan findings. CONCLUSION: Available data do not permit prediction of which LERVG are immune from missed lesions in a duplex scan surveillance protocol. This suggests to us that arteriography is mandatory before LERVG revisions.

Sleep deprivation can attenuate light-induced phase shifts of circadian rhythms in hamsters.

To determine whether sleep deprivation (SD) affects the response of circadian rhythms to light, hamsters were forced to walk on a slowly rotating treadmill for 6 or 24 h, ending early in the night, with or without a light pulse during the last 30 min. SD alone did not produce a significant phase shift. Light pulses (300 and 50 lx) alone induced significant delay shifts (55 and 35 min, respectively). Twenty-four hours SD significantly attenuated the delay to brighter light and 6 h SD significantly attenuated the delay to moderate light. Sleep loss or attendant low-intensity continuous activity appear to modulate the response of the hamster circadian system to light.

Prospective comparison of infrainguinal bypass grafting in patients with and without antiphospholipid antibodies.

PURPOSE: The antiphospholipid antibodies (APL)-anticardiolipin antibodies (ACL) and lupus anticoagulant (LA)-are widely believed to be associated with decreased lower extremity bypass graft patency rates. To date, no prospective cohort study has confirmed this assumption. A prospective comparison of the result of infrainguinal revascularization procedures performed since 1990 in patients with and without APL forms the basis of this report. METHODS: Patients who underwent elective infrainguinal bypass procedures from 1990 to 1994 were evaluated for hypercoagulable states (ACL, LA, protein C, protein S, and antithrombin III). Patient data were prospectively entered in a computerized vascular registry, and postoperative follow-up was maintained for life. Graft patency, limb salvage, and patient survival rates were calculated by life-table methods. RESULTS: Three hundred twenty-seven lower extremity bypass grafting procedures were performed in 262 patients. APLs were present in 83 patients (32%); 70 patients (84%) had ACLs only, 11 patients (13%) had LA only, and two patients (3%) had both ACLs and LA. There was no significant difference between APL-positive and APL-negative patients with respect to demographics, associated medical conditions, indication for operations, and type of procedures performed. More patients who had APLs had warfarin treatment after surgery (43% vs 24%, p = 0.002). Life table 4-year primary patency rates showed minimal difference (APL-positive, 43%; APL-negative, 59%; p = 0.087), and no significant difference was noted in assisted primary patency rates (APL positive, 72%; APL negative, 73%; p = NS), limb salvage rates (APL positive, 79%; APL negative, 88%; p = NS), and patient survival rates (APL positive, 67%; APL negative, 66%; p = NS). CONCLUSIONS: APLs were found in a surprising one third of the patients who underwent leg bypass grafting procedures. The majority of APLs identified were ACLs (87%). There was minimal difference in graft primary patency rates, and no difference in assisted primary patency, limb salvage, and survival rates between patients with and without APLs who underwent leg bypass grafting procedures. The extreme morbidity rate associated with APLs in previous reports is not confirmed by this prospective study. APLs should not be regarded as a contraindication to indicated leg bypass grafting procedures.

Long-term outcome of Raynaud's syndrome in a prospectively analyzed patient cohort.

PURPOSE: Knowledge of the long-term clinical outcome of Raynaud's syndrome (RS), essential both for patient counselling and formulation of optimal therapeutic recommendations, is conspicuously deficient in current medical literature. We have prospectively monitored 1039 patients with RS, 118 (11.4%) for more than 10 years to determine whether initial characterization was able to predict outcome. METHODS: At initial presentation, patients were divided into four groups on the basis of vascular laboratory and serologic testing results: vasospastic, serologically positive (spast,sero+) and negative (spast,sero-) and obstructive, serologically positive (obst,sero+) and negative (obst,sero-). RESULTS: Connective tissue disease (CTD) was present initially in 48.6% of patients with spast,sero+ results and 72.9% of patients with obst,sero+ results. Of the remaining patients in these groups, progression to CTD during follow-up occurred in 16.4% of patients with spast,sero+ results and 30.4% of patients with obst,sero+ results. In the > 10-year follow-up group, progression to CTD occurred in 81.8% of patients in the obst,sero+ group. Progression to CTD occurred in 2.0% of patients in the spast,sero-group and 8.5% of patients in the obst,sero- group. Digital ulcers occurred in 15.5% of patients in the spast,sero+ group, 5.2% of patients in the spast,sero- group, 55.6% of patients in the obst,sero+ group, and 48.2% of patients in the obst,sero- group. Digital or phalangeal amputations were required in 1.4%, 1.6%, 11.6%, and 19.0% of these patients, respectively. CONCLUSIONS: The long-term outcome of patients with RS can be predicted by initial serologic studies and separation into vasospastic and obstructive categories. Initial serologic positivity strongly predicts the development of CTD. Initial vascular laboratory classification of obstructive RS strongly predicts digital ulcerations, which occurred in half of these patients regardless of initial serologic study results. Amputations were required in 10% to 20% of patients with obstructive RS. These occurrences did not increase with increased duration of disease. Ulcerations and amputations were rare in patients initially with vasospastic RS.

Current management of Raynaud's syndrome.

Raynaud's syndrome affects 20% to 25% of the population in cool, damp climates. Although its etiology and pathophysiology are poorly understood, treatment options do exist. For mild cases, the wearing of gloves, cold avoidance, tobacco cessation, and assurance that this is a nuisance condition that will not lead to finger amputation are often all that is required. Patients who fail this protocol are treated with extended-release nifedipine, 30 mg, at bedtime. In our experience, 70% to 80% respond with a decrease in severity and frequency of attacks, but 20% to 50% develop intolerable side effects. If nifedipine fails, we consider another calcium-channel blocker, an ACE inhibitor, or Dibenzyline. Biofeedback is offered to patients, but in our experience few are interested. Patients with digital ulceration are treated with nifedipine, pentoxifylline, and antibiotics as needed. We recommend soap-and-water washes and either a damp dressing or Silvadene cream. If there is chronic non-healing or intractable pain, we have on occasion performed a fingertip amputation. Although these do not tend to heal promptly, they generally do heal with time and provide excellent pain relief. We have not performed upper extremity sympathectomy for nonhealing finger ulcers in more than 20 years.

Induction of tryptophan catabolism is the mechanism for gamma-interferon-mediated inhibition of intracellular Chlamydia psittaci replication in T24 cells.

Human uroepithelial (T24) cells were incubated for 24 h in the presence of various concentrations of human recombinant gamma interferon (Hu-rIFN-gamma) and then infected with the 6BC strain of Chlamydia psittaci. This resulted in a reduction of intracellular chlamydial inclusion development in proportion to the concentration of Hu-rIFN-gamma present when Giemsa-stained cells were examined by light microscopy 24 h after infection. When tryptophan was added to Hu-rIFN-gamma-treated cells just after infection, reversal of the Hu-rIFN-gamma-mediated inhibition occurred in proportion to the concentration of tryptophan added. Addition of either isoleucine or lysine did not result in reversal of the antichlamydial state. Transport of L-[3H]tryptophan into acid-soluble intracellular pools was found to be greatly enhanced in Hu-rIFN-gamma-treated T24 cells compared with the rates measured for untreated cells. Transport of [3H]leucine was not increased in treated cells. Cells treated with Hu-rIFN-gamma also degraded L-[3H]tryptophan to catabolites that cochromatographed with N-formylkynurenine and kynurenine as measured by high-performance liquid chromatography. We conclude that Hu-rIFN-gamma-mediated inhibition of intracellular C. psittaci replication in T24 cells occurs by depletion of the essential amino acid tryptophan, most likely via the induction of indoleamine-2,3-dioxygenase, the initial enzyme of tryptophan catabolism.