A distinctive form of human chorionic gonadotropin beta-subunit-like material produced by cervical carcinoma cells.

The DoT and CaSki human cervical carcinoma cell lines ectopically produce material immunologically similar to the beta-subunit of human chorionic gonadotropin (hCG beta). Culture fluids were analyzed by gel filtration chromatography and radioimmunoassay (RIA) using (a) antiserum directed to conformation-specific (core-directed) determinants not involving the carboxyl-terminal peptide (CTP) in hCG beta purified from urinary hCG (i.e., standard hCG beta) or (b) antiserum directed to the CTP in standard hCG beta. CTP-directed RIA recognized a peak of hCG beta-like immunoreactive material that eluted in the same position as standard hCG beta. However, core-directed RIA recognized additional hCG beta-like material (i.e., ectopic beta-II), most of which eluted before standard hCG beta. CaSki cells were incubated with [3H]mannose, [3H]proline, and [3H] leucine, and the spent medium was immunoprecipitated and analyzed by gel electrophoresis. Several labeled peaks were detected in the lane from the anti-hCG beta X Sepharose immunoprecipitate, one of which corresponded in mobility to standard hCG beta, with two more intense components migrating at higher apparent molecular weights. Carboxypeptidase Y digestion released only 0.2 mol equivalents each of [3H]proline and [3H]leucine from the labeled CaSki material immunoprecipitated with anti-hCG beta X Sepharose, compared to 1 mol equivalent each in similar analysis of standard hCG beta. These findings were consistent with the absence of the 4-carboxy-terminal amino acids from 80% of the hCG beta-like immunoreactive material secreted by CaSki cells. The affinity purified ectopic beta-II failed to combine with standard hCG alpha under conditions in which combination of standard hCG beta with standard hCG alpha was essentially complete. Neither aggregation nor proteolytic degradation was the cause of failure of ectopic beta-II to combine with hCG alpha. We conclude that both the DoT and CaSki cervical carcinoma cell lines secrete a distinctive form of hCG beta-like material, ectopic beta-II. Lack of recognition by CTP-directed antisera and amino acid analysis suggest that ectopic beta-II may lack the CTP, despite its apparent larger size relative to standard hCG beta.

Providers and receivers in the private psychiatric Medicaid system.

The authors investigated the credentials of foreign medical graduate (FMG) and U.S. medical graduate (USMG) psychiatrists providing a substantial amount of Medicaid care and compared them with those of a group of other psychiatric practitioners in New York City. USMGs were more likely to be Board certified, but FMGs were as likely to have APA membership, psychoanalytic training, medical school and hopsital affiliation, and fellowships. The credentials of the Medicaid psychiatrists and the group of New York psychiatrists were similar. Hispanic FMG psychiatrists provided a major service for the Spanish-speaking community, but the poor black population underused Medicaid services. Diagnosis did not appear to be influenced by racial bias.

A novel form of ectopic human chorionic gonadotrophin beta-subunit in the serum of a woman with epidermoid cancer.

A novel form of free human chorionic gonadotrophin beta-subunit (hCG beta) was found in serum from ElBre, a woman with epidermoid carcinoma of unknown origin. ElBre hCG beta was larger than standard (pregnancy urine) hCG beta when analysed by gel chromatography (apparent molecular weight 54 000 vs 44 000). This size difference appeared to be due to a larger carboxyterminal extension (CTE) of ElBre hCG beta since thermolysin cleavage of the CTE from standard hCG beta and Elbre hCG beta yielded core products of the same size. Oligosaccharides, O-linked to serine or threonine, were present in ElBre hCG beta, presumably on its CTE as judged by the complete binding of desialylated ElBre hCG beta to immobilized peanut agglutinin (this lectin is specific for terminal galactose linked beta 1----3 to N-acetylgalactosamine, a disaccharide exposed after desialylation of the O-linked oligosaccharides of standard hCG beta). ElBre hCG beta, however, was incompletely recognized by antisera specific for the CTE of standard hCG beta, especially the carbohydrate-sensitive antiserum R141. The O-linked oligosaccharides of standard hCG beta are heterogeneous in size; 13% are of the largest (hexasaccharide) form. In contrast, over 50% of the O-linked oligosaccharides in hCG beta from the JAr choriocarcinoma cell line are hexasaccharides. Like desialylated ElBre hCG beta, desialylated JAr hCG beta bound completely to peanut agglutinin, but was incompletely recognized by antisera to the hCG beta-CTE. Furthermore, JAr hCG beta was intermediate in size between standard hCG beta and ElBre hCG beta when analysed by gel chromatography (apparent molecular weight 49 000).(ABSTRACT TRUNCATED AT 250 WORDS)

Clinical and laboratory investigation of a virilized woman with placental-site trophoblastic tumor.

The novel association of virilization and placental-site trophoblastic tumor, an uncommon form of gestational trophoblastic disease (formerly called "trophoblastic pseudotumor"), is described in a 32-year old woman. Multiple agent chemotherapy lowered serum concentrations of chorionic gonadotropin (hCG) (8.7 to 2.1 ng/mL), pregnancy-specific beta 1-glycoprotein (32 to 3.9 ng/mL), and testosterone (400 to 74 ng/dL). Subsequent hysterectomy revealed a 2-cm tumor nodule within the myometrium, and one week postoperatively serum concentrations of hCG (0.5 ng/mL), pregnancy-specific beta 1-glycoprotein (1.3 ng/mL), and testosterone (20 ng/dL) had all returned to normal. Percutaneous catheterization of the ovarian veins before chemotherapy demonstrated a 50-fold elevation of ovarian vein testosterone concentrations compared with normal women, whereas ovarian vein 17 beta-estradiol concentrations were only twofold higher than normal. Direct sampling of the uterine veins at the time of hysterectomy documented testosterone and estradiol production, presumably by the placental-site trophoblastic tumor. Ovarian vein testosterone concentrations at this time were only fourfold above normal, probably the result of falling serum concentrations of hCG. Wedge biopsy of the ovaries disclosed minimal histologic changes (thecal cell luteinization, focal thecosis) compatible with hCG stimulation. Failure of the placental-site trophoblastic tumor to produce large amounts of estrogen, in contrast to normal pregnancy and hydatidiform mole, resulted in marked androgen/estrogen imbalance, high circulating concentrations of free testosterone, and virilization.(ABSTRACT TRUNCATED AT 250 WORDS)

Pedicle screw fixation for arthrodesis of the lumbosacral spine in the elderly. An outcome study.

STUDY DESIGN: An analysis of the outcome and effectiveness of instrumented arthrodesis of the lumbosacral spine in elderly patients conducted using a review of records, assessment of fusion via plain radiographs, and a two-part questionnaire. OBJECTIVE: To ascertain the outcome and efficacy of instrumented arthrodesis of the lumbosacral spine in patients 60 years of age and older. BACKGROUND DATA: From 1987 to 1991, 38 patients of at least 60 years of age underwent instrumented arthrodesis of the lumbosacral spine using the Wiltse or Selby pedicle screw fixation system (Advanced Spine Fixation Systems, Inc., Irvine, CA). Patients were considered for surgery only after attempts at conservative management, including physical therapy, medication, injection blocks, and home exercises, had proven unsuccessful. METHODS: Follow-up examinations were performed 3 months, 6 months, 1 year, and 2 years after surgery. Fusion was assessed using plain radiographs, including flexion-extension films. Inpatient and outpatient records were reviewed, and a two-part questionnaire was used to establish the effect of surgery on function and lifestyle. Thirty patients responded to the questionnaire. Follow-up observation of the patients ranged from 25 to 56 months. The mean age was 73.8 years (range, 60-90 years). RESULTS: The mean co-morbidity was 1.7. Based on the authors' method of evaluation of fusion, the fusion rate was 92%. Fifty-seven percent of the patients reported excellent or good results, 26% reported fair results, and 17% reported poor results. Functional gains of 50% or more were reported by 71% of the respondents. Female patients had significantly more complications than male patients, but reported comparable outcomes. CONCLUSION: Despite the increase in age, co-morbidity, and associated risk of perioperative complications inherent in this population, an outcome comparable with that of younger patients is reported.

Evaluation of continuous intraspinal narcotic analgesia for chronic pain from benign causes.

Intraspinal narcotic analgesia (INA) has been used for chronic pain from nonmalignant causes with moderate success. To ascertain the efficacy of the morphine pump, we reviewed the 2-year results of continuous INA in 18 patients with failed back syndrome or arachnoiditis and intractable, debilitating pain that was unrelieved by conventional means. All patients underwent a trial screening of single-dose intrathecal narcotics with good pain relief. After 2 years, 8 pumps were still functioning, 8 patients had the pump removed or turned off, and 2 patients were lost to follow-up. Our patients averaged 1.4 additional procedures or hospitalizations after initial pump insertion. Overall, only 4 patients had objective evidence of benefit from INA, for a success rate of 25%. Results of this review suggest INA should not be used for the long-term management of chronic pain from nonmalignant causes.

Isolated ectopic production of the free beta subunit of chorionic gonadotropin by an epidermoid carcinoma of unknown primary site.

Metastatic choriocarcinoma was suspected in a 39-year-old woman who presented 7 months postpartum with fatigue, pelvic pain, a massive pleural effusion, and a positive urine pregnancy test. Subsequent evaluation resulted in discovery of the isolated production of the free beta-subunit of chorionic gonadotropin (CG-beta) by a widespread, poorly differentiated epidermoid carcinoma. Chemotherapy was ineffective, the woman died, and at autopsy the primary site of the tumor could not be determined. The patient's serum (185 ng/ml) and a tumor metastasis (720 ng/g) contained large amounts of immunoactive material that diluted in parallel to CG-beta standard, but neither chorionic gonadotropin (CG), its alpha subunit, nor other placental proteins were detected. A monoclonal antibody that recognizes free CG-beta, but not intact CG, was instrumental in implicating an ectopic source of the CG-beta before a tissue diagnosis was obtained. When the patient's serum was chromatographed on a dextran gel, the CG-beta immunoactivity eluted in a position of higher apparent molecular weight than either standard CG or CG-beta, suggesting that this neoplasm secreted an altered molecular form of the CG-beta subunit.

Cervical spine fusions for trauma. A long-term radiographic and clinical evaluation.

Ninety-six successful cervical spine fusions performed for trauma, with a minimum of 5 years' follow-up, were retrospectively reviewed. Radiographic degenerative changes adjacent to fusion masses were assessed and correlated with clinical symptoms. The type of fusion, fusion extension, and final kyphosis of the involved segments were also analyzed. Twenty-eight patients had fusion masses aligned in 20 degrees or more of kyphosis. There was a significant increase in complaints of cervical pain in patients with neck fusions equal to or exceeding 20 degrees of kyphosis (P < 0.01). Evidence of mild degenerative changes adjacent to fusion masses was common, but did not correlate with symptoms.

Outcome after Wiltse pedicle screw removal.

Thirty-five patients were retrospectively reviewed after hardware removal after previous posterior lumbar spinal fusion by using Wiltse pedicle screw fixation. Pseudarthrosis was intraoperatively confirmed in 10 patients. Thirty of 35 patients were reviewed at an average of 17.5 months (range, 6-57 months). Of 30 patients, 30 had persistent back pain that limited activities and lumbar motion. Patients found to have pseudarthroses were significantly more likely to have less pain, use fewer narcotic medications, and have an improved quality of life after reoperation than patients found to have solid fusions. Postsurgical assessment of fusion is difficult, with instrumentation making exploration the most reliable method determining the state of arthrodesis. Accurate preoperative assessment of the fusion mass is the most important factor in deciding whether or not to reoperate on patients after Wiltse pedicle screw arthrodesis of the lumbar spine.

Differential regulation of hCG alpha and beta subunit mRNAs in JEG-3 choriocarcinoma cells by 8-bromo-cAMP.

The coordinate regulation of human chorionic gonadotropin (hCG) subunit synthesis by JEG-3 choriocarcinoma cells was studied at the pretranslational level. The responses of the hCG alpha and beta mRNAs were measured during stimulation with the potent cAMP analog 8-bromo-cAMP (8-Br-cAMP) using 32P-labeled hCG alpha and beta cDNA probes. The hCG alpha mRNA (850 bases) and beta mRNA (1050 bases) from JEG-3 cells were identical in size to that of their respective mRNAs from placenta, by Northern blot analysis. After 48 h of stimulation with 2 mM 8-Br-cAMP, production of immunoreactive alpha and beta subunits increased 25- and 52-fold, respectively; corresponding levels of the alpha and beta mRNAs increased 36- and 43-fold, respectively, in a dot blot hybridization assay. Total cellular protein, DNA content, and messenger RNA pools were not altered by treatment with 8-Br-cAMP. The temporal coordination of the expression of the hCG alpha- and beta-subunit genes was examined by comparing the time course of stimulation of the respective mRNAs and the production of immunoreactive subunits. The kinetic responses of the alpha and beta mRNAs differed: the increase in hCG alpha mRNA preceded the increase in hCG beta mRNA, while levels of free alpha subunit and intact hCG increased in parallel with the increase in beta mRNA. hCG alpha mRNA levels increased rapidly between 8 and 24 h after the addition of 8-Br-cAMP, and approached a plateau by 48 h. The levels of hCG beta mRNA increased steadily throughout the 8-48 h period. These results demonstrate that the cAMP analog 8-Br-cAMP differentially regulates hCG subunit biosynthesis in JEG-3 cells at a pretranslational level, and that the stimulation by 8-Br-cAMP in this system appears to be relatively selective for hCG subunits.

Pretranslational regulation of ectopic hCG alpha production in ChaGo lung cancer cells by sodium butyrate.

Ectopic production of hCG and its free alpha subunit by ChaGo lung cancer cells is stimulated by sodium butyrate. To investigate pretranslational regulation in this system, we examined the response of the hCG alpha and beta subunit mRNAs in ChaGo-K1 cells, a clone that produces free hCG alpha but no hCG or hCG beta in the basal state. When a Northern blot of total RNA from ChaGo cells was hybridized to a [32P]- labeled hCG alpha cDNA probe, a single band was detected that was identical in size (approximately 850 bases) to placental hCG alpha mRNA. RNA from butyrate-stimulated (5 mM, 24 h) ChaGo cells contained 7.7 times as much hCG alpha mRNA as RNA from control ChaGo cells. This increase appeared to be relatively selective since no difference in total polyA-containing mRNA levels was detected between butyrate-treated and control cells by [32P]oligo(dT) hybridization. In addition, no hCG beta mRNA was detected when Northern and dot blots were hybridized to an hCG beta cDNA probe. In a time course experiment, hCG alpha mRNA accumulation in butyrate-treated cells increased significantly by 8 h with a maximum increase of 6.1-fold at 24 h compared to control values. Major differences in immunoactive hCG alpha accumulation were not apparent, however, until after 24 h. These studies show that stimulation of ChaGo hCG alpha production by butyrate can be completely accounted for by pretranslational events and that failure to detect hCG or free hCG beta production by these cells is not due to poorly translatable RNA or post-translational protein degradation. Thus, exclusive ectopic production of only one of the hCG subunits is likely to be due to selective genomic expression.

Nonoperative management of upper thoracic spine fractures.

We attempted to determine if nonsurgical treatment could be successful in treating instability of upper thoracic spine fractures, which may receive some stabilization and splinting from the ribs. From 1966 to 1989, the records of all patients treated at Rancho Los Amigos Medical Center for fractures from T-1 to T-8 were reviewed. Penetrating injuries and malignant lesions were excluded. A total of 118 patients were admitted during this period; 49 patients had nonsurgical treatment. Complications included 1 patient with neurologic worsening, brace-related skin necrosis in 8 cases, and deep venous thrombosis in 12 patients. No failure of arthrodesis was noted. Rib fractures did not adversely affect late stability. We conclude that orthotic treatment of thoracic spine instability from T-1 to T-8 can be successful, especially in cases where early surgery is not possible.

Assessment of pseudarthrosis in pedicle screw fusion: a prospective study comparing plain radiographs, flexion/extension radiographs, CT scanning, and bone scintigraphy with operative findings.

Twenty-five consecutive patients who had previously undergone lumbar fusion using stainless steel pedicle screw instrumentation and complained of persistent, severe pain were identified for prospective study. All patients had been scheduled for hardware removal and fusion inspection. Studies to rule out pseudarthrosis included plain radiography, flexion and extension radiography, computed tomography, and bone scintigraphy. Each preoperative radiographic study was then evaluated in a blinded fashion by a single independent radiologist and was determined to show fusion or pseudarthrosis. Each patient then underwent surgery, at which time the pedicle screw instrumentation was removed and the fusion was inspected. Using surgical inspection as absolute evidence of fusion or pseudarthrosis, statistical analysis was undertaken to evaluate the predictive value of the radiographic studies singly and in combination. No statistically significant correlation was found.

Ectopic soft tissue calcium deposition following liver transplantation.

We observed ectopic soft tissue calcification affecting seven patients following orthotopic liver transplantation. The cause of such calcification is unknown, but potential pathogenetic factors include hyperparathyroidism, calcium administered during and following surgery, renal failure, acid-base changes and citrate in fresh frozen plasma. To investigate some of the mechanisms underlying ectopic calcification following liver transplantation, we determined preoperative levels of ionized serum calcium, phosphate, magnesium, parathyroid hormone (midmolecule assay) and 1,25-(OH)2 vitamin D in 20 patients who underwent 24 liver transplants. In addition, these parameters were measured weekly in 15 patients during the first month after liver transplantation. Preoperatively, 5 of the 20 patients had elevated serum levels of parathyroid hormone, and 9 others had low levels of 1,25-(OH)2 vitamin D. After liver transplantation, ectopic calcification was found in seven patients (47%). The organs affected in order of frequency were lungs, liver graft, colon, vascular walls, kidneys, adrenal glands and gastric mucosa. One patient with ectopic calcification of both lungs had markedly restricted pulmonary function as well as radiologic evidence of osteopenia and pathologic fractures of three vertebrae. Postoperatively, increased parathyroid hormone levels were found in all patients who developed soft tissue calcification. Parathyroid hormone levels peaked during the second week after transplantation and were higher at all times compared to subjects without calcification. Five of the seven patients with ectopic calcification had associated renal failure. Individuals who developed calcification had received significantly more fresh frozen plasma, red blood cells and elemental calcium postoperatively, but showed no difference in serum levels of calcium, magnesium, vitamin D, total plasma CO2 or phosphate levels when compared to patients without calcification.(ABSTRACT TRUNCATED AT 250 WORDS)

Medicaid-funded private psychiatric care in New York City. The role of foreign-trained physicians.

Data were obtained from the tax records and the Professional Registry maintained by the New York City Department of Health as well as from the Biographical Directory of the American Psychiatric Association to determine which psychiatrists were providing care under the Medicaid Program and how they compare with the pool of psychiatric practitioners in New York City. The data reveal that psychiatrists educated in foreign medical schools provide disproportionately more care to Medicaid recipients than would be anticipated from their numbers, and are a majority of those who received more than +30,000 in payments in 1976. Furthermore, these psychiatrists account for 80 per cent of those delivering care at the two largest "shared health facilities," commonly referred to as "Medicaid mills." These findings indicate that although the Title XIX Program has facilitated the access of the poor to the private psychiatric sector, in New York City their access is biased toward treatment by foreign-educated psychiatrists.