Prevention of experimental autoimmune myasthenia gravis by a monoclonal antibody to a complementary peptide for the main immunogenic region of the acetylcholine receptors.

We have previously reported that a complementary peptide (denoted RhCA 67-16), encoded by RNA complementary to that of the Torpedo acetylcholine receptor (AChR) main immunogenic region (MIR), AChR residues alpha 61-76, induces polyclonal and monoclonal Ab reactive with Ig against the AChR MIR. RhCA 67-16 vaccination also protected against the development of experimental autoimmune myasthenia gravis (EAMG) in Lewis rats. In the present report, we found that a mAb (denoted TCM 240, IgG1 kappa) against RhCA 67-16 recognized three different idiotypic Ab (mAb 6, mAb 35, and mAb 198), which were previously reported by others to recognize the AChR MIR and to cause EAMG. Based on these results, TCM 240 was tested for prophylactic effects in EAMG. EAMG induced passively by mAb 35 was inhibited by simultaneous injection with TCM 240. The disease severity was inversely paralleled by the ratio of mAb 35 to TCM 240. EAMG induced by immunization with purified native Torpedo AChR was also inhibited by TCM 240, but not a control mAb. The inhibitory effect of TCM 240 on actively induced EAMG occurred without significantly lowering the overall AChR Ab levels, which indicates a limited repertoire of disease-causing Ab in EAMG and perhaps MG. Such findings suggest the existence of an EAMG-associated Id and also support the concept of an MIR. In a more general sense, these results demonstrate that prophylactic and perhaps diagnostic mAb for autoimmune diseases can be produced by immunization with complementary peptides for disease-associated epitopes.

Pasteurella multocida empyema: successful treatment with open thoracostomy.

Pasteurella multocida appears to be an uncommon pathogen in human thoracic empyema. The morbidity and mortality associated with these infections has been significant, presumably secondary to the elderly populations they affect, many with chronic lung disease and impaired pulmonary defenses. We report a case of pasteurella empyema treated with open thoracostomy and rib resection and advocate use of such a procedure early in the treatment of patients with this infection.

Improving diagnostic accuracy in appendicitis.

After reviewing all 123 of these patients, here are some suggestions which may improve the accuracy of diagnosis of appendicitis. 1. Proceed slowly with any patient with equivocal history and physical exam +/- WBC less than 10,000. 2. Seriously consider U.T.I. or other renal pathology in patients with greater than 20 RBC +/or greater than 30 WBC/hfp (w/bacteria) as cause of RLQ pain, rather than appendicitis; i.e. only 1 of 81 patients with appendicitis had a coexistent U.T.I. 3. Be aware that pain starting in the RLQ is less common in appendicitis than in other conditions mimicking appendicitis. 4. Be wary of all women presenting with RLQ pain on days 1 through 10 of their menstrual cycle. 5. Consider a barium swallow or enema study in patients in categories 1-4 above looking for a normally filled appendix while a) observing patient and b) awaiting outstanding lab results (i.e. ur. cult., cerv. os cult., etc.). 6. Follow closely all patients in all of the above categories and operate for worsening condition. 7. Require classic or near classic history and physical findings in patients with WBC less 10,000 suspected of having appendicitis, prior to surgery. Footnotes to these suggestions are as follows: 1. Understand that following these suggestions may result in an increase in the incidence of perforation coincident with an increase in diagnostic accuracy. 2. Be less hesitant to operate on patients over 50 y.o. because of a) their frequent atypical presentations, and b) the known higher incidence of perforation in this age group.(ABSTRACT TRUNCATED AT 250 WORDS)

Pulmonary dirofilariasis. The largest single-institution experience.

Pulmonary dirofilariasis caused by Dirofilaria immitis, the dog heartworm, is a rarely reported pulmonary lesion. It appears as a solitary pulmonary nodule, and the diagnosis is not established until thoracotomy and subsequent histologic examination of the specimen are performed. Sporadic reports of pulmonary dirofilariasis in the United States total only 70 cases. The six resections of pulmonary dirofilariasis at the Ochsner Clinic represent the largest reported series of cases originating at a single institution. We present an overview of the pathogenesis of this disease, its clinical manifestations, pathologic and epidemiologic features, and geographic distribution. The prevalence of pulmonary dirofilariasis appears to be increasing; hence, thoracic surgeons and pathologists need to be alert to this cause of granulomatous pulmonary lesions.

Characterization of the cyclic AMP-independent actions of somatostatin in GH cells. I. An increase in potassium conductance is responsible for both the hyperpolarization and the decrease in intracellular free calcium produced by somatostatin.

The neuropeptide somatostatin causes membrane hyperpolarization and reduces the intracellular free calcium ion concentration ([Ca2+]i) in GH pituitary cells. In this study, we have used the fluorescent dyes bisoxonol (bis,-(1,3-diethylthiobarbiturate)-trimethineoxonol) and quin2 to elucidate the mechanisms by which these ionic effects are triggered. Addition of 100 nM somatostatin to GH4C1 cells caused a 3.4 mV hyperpolarization and a 26% decrease in [Ca2+]i within 30 s. These effects were not accompanied by changes in intracellular cAMP concentrations and occurred in cells containing either basal or maximally elevated cAMP levels. To determine which of the major permeant ions were involved in these actions of somatostatin, we examined its ability to elicit changes in the membrane potential and the [Ca2+]i when the transmembrane concentration gradients for Na+, Cl-, Ca2+, and K+ were individually altered. Substitution of impermeant organic ions for Na+ or Cl- did not block either the hyperpolarization or the decrease in [Ca2+]i induced by somatostatin. Decreasing extracellular Ca2+ from 1 mM to 250 nM abolished the reduction in [Ca2+]i but did not prevent the hyperpolarization response. These results show that hyperpolarization was not primarily due to changes in the conductances of Na+, Cl-, or Ca2+. Although the somatostatin-induced decrease in [Ca2+]i did require Ca2+ influx, it was independent of changes in Na+ or Cl- conductance. In contrast, elevating the extracellular [K+] from 4.6 to 50 mM completely blocked both the somatostatin-induced hyperpolarization and the reduction in [Ca2+]i. Furthermore, hyperpolarization of the cells with gramicidin mimicked the effect of somatostatin to decrease the [Ca2+]i and prevented any additional effect by the hormone. These results indicate that somatostatin increases a K+ conductance, which hyperpolarizes GH4C1 cells, and thereby secondarily decreases Ca2+ influx. Since the somatostatin-induced decrease in [Ca2+]i is independent of changes in intracellular cAMP levels, it may be responsible for somatostatin inhibition of hormone secretion by its cAMP-independent mechanism.

History and evolution of peptic ulcer surgery.

The development of peptic ulcer surgery is traced from 1881 and Billroth until the present. Discussion of the physiologic basis for gastric resection, the several types of vagotomy, and antrectomy is presented as conceived by the surgeons who originated these operations. Treatment of the complications of peptic ulcer surgery is discussed as well as the current diagnostic and therapeutic approach to the Zollinger-Ellison syndrome.

An analysis of 15 cases of gallbladder carcinoma.

Fifteen cases of cancer of the gallbladder are presented. Unfortunately, this lesion is not diagnosed until well advanced and survival rates are consequently poor. Cholelithiasis is usually present. Gallbladder carcinoma is a disease of older people. Because of the much higher morbidity and mortality of cholelithiasis in this age group, prophylactic cholecystectomy in good risk surgical patients is recommended.