Detection of Antibodies in Human Sera to Streptococcal Groups A and C Carbohydrates by a Radioimmunoassay

The human lymphokine, leucocyte migration-inhibitory factor (LIF), appears to be a serine esterase and protease by virtue of its susceptibility to the irreversible enzyme inhibitor, phenylmethylsulfonyl fluoride (PMSF), and by the ability of arginine esters and amides to protect LIF against PMSF-induced inactivation. In this paper, three methods are described by which putative substrates for LIF may be investigated. Thus, molecules satisfying the substrate specificities of this lymphokine should (1) protect LIF against inactivation by PMSF, (2) reduce LIF activity in vitro on polymorphonuclear leucocytes, and (3) reduce the esterolytic activity of purified LIF-rich supernatants. The first two reactions were tested by means of the leucocyte migration agarose technique; the third reaction was tested by a sensitive enzyme assay using tritiated tosyl arginine methyl ester as substrate. Guanosine 3',5'-cyclic monophosphoric acid, which is capable of protecting LIF against PMSF-induced inhibition, also inhibited the esterolytic activity of the purified LIF preparation. Four synthetic oligopeptide substrates for trypsin, thombin and plasmin were investigated. Only one, the thrombin- and trypsin-specific benzoyl-phenylalanyl-valyl-agarine-p-nitroanilide, possessed high affinity for the LIF molecule and may therefore prove to be a potent substrate for this lymphokine.     

Tropane alkaloid production in transformed root cultures of brugmansia Candida

Transformed root cultures of BRUGMANSIA CANDIDA were established by infection with AGROBACTERIUM RHIZOGENES LBA 9402. Several clones with different growth index and tropane alkaloid pattern and content were obtained and two were examined in depth. The alkaloid content and pattern changed during the time course. At 21 days of culture clone 1 revealed an alkaloid spectrum dominated by 3alpha-acetoxytropane (about 50% of the total alkaloid) and hyoscyamine (about 25%), with a ratio of hyoscyamine to scopolamine of 11.2. In clone 40 this ratio was 1.5 and the content of 3alpha-acetoxytropane was low (2%). The maximum concentrations of hyoscyamine were obtained at 3 weeks of culture, and were 700 and 500 microg/g FW in clone 1 and 40, respectively.     

Evaluation of biologic end points and pharmacokinetics in patients with metastatic breast cancer after treatment with erlotinib, an epidermal growth factor receptor tyrosine kinase inhibitor.

PURPOSE: To evaluate changes in epidermal growth factor receptor (EGFR) phosphorylation and its downstream signaling in tumor and surrogate tissue biopsies in patients with metastatic breast cancer treated with erlotinib, an EGFR tyrosine kinase inhibitor, and to assess relationships between biomarkers in tumor and normal tissues and between biomarkers and pharmacokinetics. PATIENTS AND METHODS: Eighteen patients were treated orally with 150 mg/d of erlotinib. Ki67, EGFR, phosphorylated EGFR (pEGFR), phosphorylated mitogen-activated protein kinase (pMAPK), and phosphorylated AKT (pAKT) in 15 paired tumor, skin, and buccal mucosa biopsies (at baseline and after 1 month of therapy) were examined by immunohistochemistry and analyzed quantitatively. Pharmacokinetic sampling was also obtained. RESULTS: The stratum corneum layer and Ki67 in keratinocytes of the epidermis in 15 paired skin biopsies significantly decreased after treatment (P = .0005 and P = .0003, respectively). No significant change in Ki67 was detected in 15 tumors, and no responses were observed. One was EGFR-positive and displayed heterogeneous expression of the receptor, and 14 were EGFR-negative. In the EGFR-positive tumor, pEGFR, pMAPK, and pAKT were reduced after treatment. Paradoxically, pEGFR was increased in EGFR-negative tumors post-treatment (P = .001). Although markers were reduced in surrogate and tumor tissues in the patient with EGFR-positive tumor, no apparent associations were observed in patients with EGFR-negative tumor. CONCLUSION: Erlotinib has inhibitory biologic effects on normal surrogate tissues and on an EGFR-positive tumor. The lack of reduced tumor proliferation may be attributed to the heterogeneous expression of receptor in the EGFR-positive patient and absence of target in this cohort of heavily pretreated patients.     

Surgical risks and outcome of pancreas retransplants

BACKGROUND: The increased popularity of pancreas transplants has led to an increased number of potential candidates for retransplants after the initial graft has been lost to technical failure or rejection. We studied a group of recipients who underwent pancreas transplants at a single center to determine whether retransplant recipients were at higher risk of complications. METHODS: Between June 1, 1994, and Dec 31, 1997, a total of 213 pancreas transplants were performed at the University of Minnesota. Of these, 187 were primary transplants and 26 were retransplants. Demographically, the two groups were not significantly different. We analyzed and compared the two groups with respect to incidence of surgical complications, graft survival rates, and patient survival rates. RESULTS: Surgical complications such as bleeding and vascular thrombosis were slightly more common after retransplants, but this trend did not quite reach statistical significance. Infectious complications and leaks were equivalent between the two groups. The incidence of acute rejection was higher after retransplants (P =.02). At 3 years posttransplant, patient survival was no different between the two groups, but pancreas graft survival was lower after retransplants (P =.08). The incidence of early graft loss (by 6 months posttransplant) was significantly higher in retransplant recipients (27% vs 14%, P =.04). CONCLUSIONS: Pancreas retransplants can be performed with a minimal increase in surgical complications. However, graft survival after retransplants is slightly inferior to that after primary transplants, probably for both immunologic and nonimmunologic reasons. Retransplants can be offered to suitable candidates, but they may require more aggressive monitoring for rejection.     

Prolonged preservation increases surgical complications after pancreas transplants

BACKGROUND: Prolonged preservation of the donor organ may result in delayed graft function or nonfunction after most organ transplants. We studied whether or not prolonged preservation increases surgical complications after pancreas transplants. METHODS: Between January 1, 1994, and September 30, 1998, a total of 294 recipients underwent cadaver pancreas transplants at our institution. Recipients were analyzed in 2 groups: those with pancreas preservation time < or = 20 hours (n = 211) versus > 20 hours (n = 83). RESULTS: Demographic data were similar between the 2 groups, except that mean donor age in the prolonged preservation group was significantly lower. Despite use of younger donors, prolonged preservation was associated with an increased incidence of surgical complications, most notably leaks, thrombosis, and wound infections. Grafts with prolonged preservation were more often noted by the transplant surgeon to be edematous after reperfusion, although the incidence of hyperamylasemia posttransplant did not differ between the 2 groups. Graft and patient survival rates also did not differ between the 2 groups. The incidence of early graft loss (< 3 months) was, however, higher in the prolonged preservation group (20.5% versus 9.0%, P = .04). CONCLUSIONS: Prolonged preservation of the donor organ increases the incidence of surgical complications after pancreas transplants. All attempts should be made to minimize preservation time, keeping it below 20 hours, if possible.     

Advances in computer-assisted single-photon emission computed tomography (SPECT) for epilepsy surgery in children

Epilepsy surgery has emerged as an important option in the treatment of children with epilepsy that is refractory to antiepileptic drug management. The cornerstone of successful surgery is accurate localization of the brain region of seizure onset. Traditional techniques of seizure onset localization, e.g. surface electroencephalography (EEG) recording and magnetic resonance imaging (MRI), allow accurate localization in a significant number of patients. When the focus of seizure onset is not apparent from these non-invasive techniques, other methods of localization, e.g. intracranial EEG recording, may be needed before resection of the focus. Single-photon emission computed tomography (SPECT) is a nuclear medicine blood-flow technique that has been used to identify a region of epileptogenic brain associated with low blood flow in the resting state (interictal SPECT) or increased blood flow at the time of seizure activity (ictal SPECT). This report describes the validation and utility of a computer-assisted method of subtracting the interictal from the ictal SPECT scans and co-registering the difference image on the MRI. This method, called subtraction ictal SPECT co-registered on MRI (SISCOM), is used in guiding the location and the extent of intracranial electrode implantation, or in obviating the need for the implantation in some cases.     

Female circumcision (female genital mutilation): a problem for brachytherapy in cervical cancer

Female circumcision is a traditional practice common in African countries. It involves partial or total removal of external female genitalia. It has led to many complications, in particular, the scarring of the external genitalia. The consequence is a very narrow introitus making the intracavitary brachytherapy treatment component difficult when these women develop cancer of cervix. We present two such cases from our institution. Our aim is to make the radiation and gynecological oncologists, both in developed and developing countries, aware of this practice and the problems they can encounter in the management of such cases. Intracavitary brachytherapy is an important component in the potentially curative role of radiation therapy for cervical cancer. Every effort should be made to ensure that the sequelae of genital mutilation does not deprive these women of the same standard of care as the general population.