The role of carbohydrate in thyrotropin action assessed by a novel approach using enzymatic deglycosylation.

Deglycosylation of thyrotropin (TSH) and gonadotropins by chemical methods virtually abolishes their biological activity without impairing receptor binding activity. Recent reports have suggested that enzymatic deglycosylation, using endoglycosidases caused a much smaller decrease, if any, in the potency of the glycoprotein hormones without altering the Vmax. However, in these studies complete removal of the carbohydrate chains from the hormones was not unequivocally documented. We have prepared completely deglycosylated bovine TSH by endoglycosidase F digestion of its subunits, which were more readily deglycosylated than the intact hormone. The deglycosylated subunits were separated from any incompletely digested subunits by concanavalin A affinity chromatography. Carbohydrate compositional analysis, using a highly sensitive pulsed amperometric detection method coupled to ion-exchange high performance liquid chromatography, was performed to ascertain the complete removal of the glycan moieties from the subunits. The deglycosylated subunits thus prepared were recombined to obtain deglycosylated TSH dimer. Receptor binding activity of bTSH was minimally affected by the carbohydrate removal. In an in vitro bioassay using stimulation of cyclic AMP production in FRTL-5 cells, deglycosylated bTSH showed reduced activity with a potency 5-10-fold lower than that of control, although the Vmax remained unaltered. In contrast, the deglycosylated bTSH showed a reduction in Vmax, when assayed for its adenylyl cyclase stimulating activity in bovine thyroid membranes. Previous reports using chemical methods have apparently overestimated the effects of deglycosylation, probably because of altered protein conformation, while those using endoglycosidases have apparently underestimated these effects, probably because of incomplete deglycosylation.

The closure index: prediction of long-term patency of femoropopliteal vein grafts.

Of 227 reversed saphenous vein femoropopliteal graft procedures performed between January 1, 1974, and December 31, 1978 limbs (72 patients) and postoperative angiograms (37% of total) were reviewed to assess the influence of graft diameter, length, and runoff on patency rates. Patient characteristics were as follows: mean age was 64 years; 73% were men; 22% were diabetics; and 68% had ischemia as the indication. Patients were followed from 26 to 86 months (mean 52 months). Patency of grafts was assessed by physical examination or arteriography and evaluated by the life-table method. Postoperative angiograms were reviewed, and the diameter and length of the vein graft, as well as the diameter and number of runoff vessels, were noted. These variables were then related by the closure index (CI). Limbs were stratified into three groups: group I--CI less than equal to 50, 51 limbs; group II--50 less than CI less than 100, 22 limbs; and group III--CI greater than equal to 100, 12 limbs. Cumulative patency rates at 3 and 5 years, respectively, were as follows; total group, 60.6% and 52.3%; group I, 71.1% and 59.6%; group II, 47.7% and 47.7%; and group III, 15.6% at 3 years. Many factors cause graft failure. Between 30 days and 5 years, thrombosis of the graft is promoted by stasis. Low-flow velocity is most often associated with a "mismatch" of graft diameter and length to runoff. Patients with a CI of 50 or lower have a 72% chance of prolonged graft patency, but in those with a CI of 100 or higher, graft failure within 1 year is to be expected. The CI enables the surgeon to predict the likelihood of long-term patency of femoropopliteal grafts.

Failure of autogenous reversed saphenous vein femoropopliteal grafting: pathophysiology and prevention.

As part of a study of various clinical, pathologic, and hemodynamic factors on both short- and long-term patency of autogenous reversed saphenous vein femoropopliteal bypass grafts, an early and recent series of patients from Yale University School of Medicine is compared with four other index series. Review and comparison reveals a well-recognized pattern of graft failure that occurs in three definable periods. The closure rate differs between periods and among series and allows a delineation of the responsible factors. Improvement in long-term cumulative patency rate depends on an understanding of the factors responsible for vein graft failure and the methods for their elimination or control.

Splenic abscess caused by Propionibacterium acnes.

A 59-year-old male diabetic was admitted with an acute myocardial infarction and had recurrent. Propionibacterium acnes bacteremia. Fifteen months after the initial admission a splenectomy was required for removal of a large splenic abscess caused by P. acnes. Although this organism represents part of the normal skin flora, its presence of blood cultures requires serious evaluation since it may signify clinical disease, not merely contamination of blood cultures by skin flora.

Effect of hemorrhagic hypotension and hypoventilation on lower esophageal sphincter pressure.

Dysfunction of the lower esophageal sphincter has been demonstrated in the cat shock model. Analogies have been drawn to reflux and aspiration in the critically ill patient. In a cat shock model, lower esophageal sphincter pressure is reduced and response to bethanechol is impaired. Upon resuscitation to basal state with heparinized shed blood, the lower esophageal basal pressure returns to normal values, and response to bethanechol is restored. This model may explain reflux and aspiration in the critically ill patient.

Air entrapment as a cause of transient cardiac pacemaker malfunction.

Air within a pacemaker pocket may cause transient malfunction of a replacement unipolar cardiac pacemaker. This was noted in a patient in whom entrapped air prevented tissue contact of the anode, resulting in complete cessation of myocardial stimulation and absence of an electrocardiographic pacemaker artifact. Methods for avoiding this complication are proposed.

Microvascular procedures in the management of lymphedema.

The burgeoning field of lymphatic research, and the applications of surgical and microsurgical techniques to the problem of lymphedema have been briefly reviewed. The chronicity of this symptom complex and the relative sparsity of cases in developed countries make controlled clinical trials of treatment unfeasable and comparisons of present regimens difficult. However, continued investigation will undoubtedly be fruitful.