[Cancer rehabilitation in the Federal Republic of Germany--a critical review from the perspective of rehabilitation psychology]. Against the background of a common criticism of the rehabilitation system, the situation of rehabilitation research and practice in oncology is reviewed. A lack of efforts aimed at vocational rehabilitation as well as the main emphasis in inpatient services is criticized. Till now, outpatient services as well as psychosocial rehabilitation care are not as well established, as they should be with regard to provide assistance in coping with the disease and in adapting to the various disabilities may be followed by cancer. As rehabilitation research in oncology is still at its very beginning, we know little about the acceptance of rehabilitation measures as well as the rehabilitation process in its correlation between outcome criteria. Our own pilot study provides first results concerning vocational rehabilitation and acceptance of medical rehabilitation services. As conclusion, we need more elaborated research in oncological rehabilitation for optimizing and further developing rehabilitation care system especially with respect to outpatient and psychosocial services.


Water-filtered infrared-A radiation: a novel technique to heat superficial tumors. A novel device consisting of an infrared-A (= ultrared-A) radiation source equipped with a water filter in the radiation path is described which allows for the therapeutic heating of superficial experimental and human tumors. Preliminary studies with agar phantoms showed that heating in the presence of the water-cuvette avoids intolerable overheating in the very superficial layers. This effect can be further enhanced by surface cooling with room air such that a stratification of the temperature distribution can be achieved. In subsequent experiments, temperature distributions were recorded in the x-, y- and z-axis of superficial rodent tumors. The results obtained confirm those from the phantom experiments, showing that therapeutically relevant temperatures (T > or = 42 degrees C) could be achieved through the tumor mass to a depth of approximately 1.2 cm. Temperature homogeneity is comparable to that seen in superficial tumors undergoing water-bath hyperthermia. This novel technique has proved to be reliable, is well-tolerated, is easy to apply, and is easily accessible to a larger number of potential users for the local heating of superficial malignancies.


[How tolerant are partial dose values? Some additional remarks on the concept of a tolerance dose]. By means of the NSD formula and its modifications (CRE, TDF) evaluated from radiotherapy experience by Ellis, it is possible to estimate the acceptance of applied radiotherapy and fractionation scheme. Because the parameters of the Ellis formula are calculated from patients data, they show a dispersion as usually in biological systems. These dispersions are considered as entrance error. In mathematical transformations errors are multiplied according to the principle of superposition of errors. Especially when judging tolerance values of organs of risk the dispersion is quite important. The problem of dispersion of resulting partial tolerance values is demonstrated by some examples of clinical cases.


Elevated intraocular pressure, pigment dispersion and dark hypopyon in endogenous endophthalmitis from Listeria monocytogenes. Listeria monocytogenes endophthalmitis occurred in an immunologically competent patient with no identifiable extraocular septic focus. The patient presented with a dark hypopyon and markedly elevated intraocular pressure, and the diagnosis was established by culture and histopathologic examination of ocular fluid. Four of the fourteen reported cases of Listeria monocytogenes endophthalmitis also presented with a dark hypopyon, and all cases had markedly elevated intraocular pressure. The presence of a dark hypopyon and elevated intraocular pressure may indicate endogenous intraocular infection with Listeria monocytogenes, even in an apparently healthy host.


Multiple cranial neuropathies: presenting signs of systemic lymphoma. A 58-year-old man four years after orthototic liver transplantation presented with a mental neuropathy, multiple ocular motor nerve palsies, and an upper extremity motor neuropathy. Serial neuroimaging, cerebrospinal fluid analysis, total body computerized tomography and paraesophageal needle biopsy failed to reveal the underlying etiology. Sural nerve biopsy showed endoneurial perivascular infiltration with lymphoid cells, and bone marrow biopsy confirmed the diagnosis of a Burkitt's-type lymphoma. Systemic lymphoma with neural infiltration should be suspected in the immunosuppressed patient who presents with cranial or peripheral neuropathies.


Disc swelling: a tall tail?

Disc swelling: a tall tail? A 30-year-old man presented with monocular visual loss secondary to chronic papilledema, due to an ependymoma involving the spinal cord. No other neurological symptoms were present at the time. Initial neuroradiologic tests as well as laboratory investigations were negative, except for elevated pressure and protein concentration of his cerebrospinal fluid. In spite of intensive investigation, the diagnosis of a spinal cord tumor was delayed for approximately 12 months until he presented with neurologic symptoms attributable to a spinal cord lesion. This is only the fourth case reported of a spinal cord tumor associated with papilledema presenting with visual loss, without any other manifestations of either elevated intracranial pressure, or spinal disease. Possible mechanisms for elevated intracranial pressure in cases of spinal cord tumors are reviewed.


Remembrance of Hans Goldmann, 1899-1991. Professor Hans Goldmann died in Bern on November 19th, 1991 at the age of 92 years. His outstanding intellectual capacity was discovered at an early age and demonstrated throughout his life. He was appointed as teaching assistant of the famous A. Cermak von Seysenegg, Chairman of the Institute of Physiology of the German Charles University in Prague. During his stay at the University of Prague, he was influenced by the famous people of his time, such as Einstein (physicist), Mach (physicist and psychophysicist), Lorenz (behavioral scientist), Popper (philosopher), Schlick (physicist and philosopher), Hering (physiologist), and others. Goldmann absorbed the essence of these disciplines to a very large extent. This, together with his remarkable intellect, enabled him to produce outstanding research work within a large spectrum of sciences more or less directly related to ophthalmology. Goldmann became known in particular for his exceptional and fundamental work on perimetry and glaucoma and he managed to cast his basic insight into practical, easy-to-operate, high-precision diagnostic instruments which, several decades after their invention, are still used by every ophthalmologist. He will enter history as one of the very great pioneers in ophthalmology.


Prospective study of the use of intraarterial secretin injection and portal venous sampling to localize duodenal gastrinomas. Duodenal gastrinomas producing Zollinger-Ellison syndrome (ZES) are rarely imaged on preoperative studies. Measurement of serum gastrin levels by transhepatic portal venous sampling (PVS) or by sampling from hepatic veins after intraarterial secretin injection have been advocated as useful tests to identify these tumors before operation. As part of a prospective study, selective intraarterial secretin injection has been performed in 36 consecutive patients with ZES, PVS has been performed in 30 of these patients, and the results have been compared. Gastrinomas were found at laparotomy in 33 of 36 patients (92%). Duodenal tumors were found in 18 patients (50%). The remaining patients had liver, pancreatic, or nodal disease (n = 15). Thirty-two of 36 patients (89%) had positive results with intraarterial secretin injection study, whereas 18 of 30 (60%) had a positive PVS gradient (p = 0.02, Fisher's exact test). The most common positive gradient with intraarterial secretin injection was found with injections of the gastroduodenal artery, and the most common positive gradient with PVS was found in the inferior pancreaticoduodenal (IPDV) or superior pancreaticoduodenal vein (SPDV). Fourteen of 18 (78%) patients with duodenal gastrinomas had a positive GDA injection, whereas five of 18 (28%) without duodenal tumors had a positive GDA injection (p = 0.006). Five of 16 patients with duodenal gastrinomas had a positive gradient in the IPDV or SPDV, whereas four of 14 without duodenal tumors had a positive gradient in the IPDV or SPDV (not significant). Intraarterial secretin injection is more sensitive than PVS at localizing duodenal gastrinomas and should replace PVS in patients with ZES and occult tumors.


Occult functioning insulinomas: which localizing studies are indicated? An occult insulinoma refers to a biochemically proven tumor with an anatomic site that remains indeterminate before operation. The amount of radiologic localization for such patients is debatable. Sixty-five patients with sporadic insulinomas were surgically treated at the Mayo Clinic between January 1980 and December 1990. True occult tumors were present in 31% of these patients (n = 20). Thirty-eight negative preoperative localization studies were performed, with 10 patients undergoing more than one study. A benign adenoma was found in 19 patients when they underwent exploratory operation, whereas one patient had malignant disease with hepatic metastases. Thirteen patients underwent intraoperative ultrasonography with a 7.5 MHz real-time high-resolution transducer. Solitary lesions were successfully removed either by enucleation or by distal pancreatectomy in all 19 patients with benign disease. This high success rate in the management of occult insulinomas suggests that extensive preoperative radiologic investigation is neither indicated nor cost-effective.


Prospective study of aggressive resection of metastatic pancreatic endocrine tumors. Because metastatic pancreatic endocrine tumors (MPET) have a poor prognosis, 17 patients with potentially resectable MPET were prospectively studied to define the efficacy of aggressive resection. Patients underwent resection when the full extent of MPET was deemed operable after imaging studies were obtained. Two patients underwent three reoperations for recurrent tumor. MPET were completely excised in 16 of 20 cases by major resections of liver, viscera, and nodes, with no operative mortality. Survival was 87% at 2 years and 79% at 5 years with mean follow-up of 3.2 years. Median imaging disease-free interval was 1.8 years, and four of 17 patients remain biochemically cured. After aggressive resection patients with MPET limited in extent had higher survival than patients with extensive MPET (p < 0.019). In a nonrandomized cohort of 25 patients with inoperable tumor, survival was 60% at 2 years and 28% at 5 years. In select patients MPET can be resected safely with a favorable outcome; most patients will experience recurrence, but some may be cured. Resection of extensive MPET does not appear to improve survival. Resection of limited MPET should be considered as life-extending and potentially curative therapy.


Posterior capsule opacification.

Posterior capsule opacification. A complication of extracapsular cataract extraction with or without posterior chamber intraocular lens (PC-IOL) implantation is posterior capsule opacification. This condition is usually secondary to a proliferation and migration of residual lens epithelial cells. Opacification may be reduced by atraumatic surgery and thorough cortical clean-up. Clinical, pathological and experimental studies have shown that use of hydrodissection, the continuous curvilinear capsulorhexis and specific IOL designs may help reduce the incidence of this complication. Capsular-fixated, one-piece all-polymethylmethacrylate PC-IOLs with a C-shaped loop configuration and a posterior convexity of the optic are effective. Polymethylmethacrylate loops that retain "memory" create a symmetric, radial stretch on the posterior capsule after in-the-bag placement, leading to a more complete contact between the posterior surface of the IOL optic and the taut capsule. This may help form a barrier against central migration of epithelial cells into the visual axis. Various pharmacological and immunological methods are being investigated but conclusive data on these modalities are not yet available.


A randomized, prospective trial of postoperative somatostatin analogue in patients with neuroendocrine tumors of the pancreas. Pancreatic surgery is not uncommonly complicated by prolonged pancreatic drainage and fistula. Octreotide decreases pancreatic exocrine function and has been reported to improve closure of pancreatic and intestinal fistulae. This randomized, prospective trial was designed to evaluate the efficacy of postoperative octreotide in reducing pancreatic drainage and complications after resection of neuroendocrine tumors of the pancreas. Patients with neuroendocrine tumors of the pancreas were entered into the study and randomized after operation to receive octreotide 150 micrograms subcutaneously every 8 hours or saline solution subcutaneously every 8 hours in a double-blinded fashion. Daily pancreatic drainage, total drainage, number of days to drain removal, and complications were recorded. Ten patients were given octreotide; eleven patients were given saline solution. The number of days to drain removal, daily drainage, and total drainage were not significantly different. Complications related to pancreatic drainage were not significantly different. Octreotide is not indicated for the routine postoperative management of patients with neuroendocrine tumors of the pancreas.


Neuroendocrine carcinomas of the stomach: a clinicopathologic evaluation. The purpose of this study was to determine by immunocytochemistry the relative incidence and clinicopathologic characteristics of neuroendocrine carcinomas of the stomach. Sections from paraffin blocks from 81 patients who had undergone resection of carcinomas of the stomach were immunostained with a battery of neuroendocrine differentiation markers and with A-80, a marker of exocrine differentiation. The clinical and pathologic data of the 12 patients diagnosed with neuroendocrine carcinomas of the stomach were analyzed. The 10 men and two women ranged from 53 to 81 years of age (median, 69 years). Procedures performed included distal subtotal gastrectomy in eight patients and total gastrectomy in four patients. Pathologic stages were stage I, one patient; stage III, four patients; and stage IV, seven patients. Metastatic sites included regional nodes, 11 patients; liver, four patients; and bone, one patient. Adjunct treatment included multiagent chemotherapy plus radiotherapy, four patients; and only radiotherapy, one patient. Eleven patients died of disease 1 to 27 months after diagnosis with an overall median survival of 15 months. Three groups of neuroendocrine carcinomas were identified based on immunostaining patterns. These included pure neuroendocrine carcinomas, two patients; neuroendocrine carcinomas with occasional exocrine cells, three patients; and mixed neuroendocrine-exocrine carcinomas, seven patients. (1) The relative incidence of neuroendocrine differentiation in carcinomas of the stomach is higher than is generally recognized. (2) Neuroendocrine gastric carcinomas behave aggressively and display numerous structural and functional similarities with their colonic, extrahepatic biliary tract, and pulmonary counterparts.


Bombesin stimulates growth of human gastrinoma. We have previously reported the first establishment and characterization of a functioning human gastrinoma (PT) xenograft. Bombesin, the equivalent of the mammalian gastrin-releasing peptide, has trophic effects on normal and neoplastic tissues of the gastrointestinal tract; the effects of gut hormones on the growth of gastrinoma are not known. The purpose of this study was twofold: (1) to determine the presence of various gut peptides in PT and (2) to determine the effect of bombesin on the growth of PT xenografts. PT tumors were examined for expression (mRNA and protein) of various gut peptides by Northern hybridization and immunohistochemistry. In addition, PT xenografts were implanted as 3 mm2 pieces bilaterally subcutaneously in athymic nude mice. Mice were divided into two groups to receive either bombesin (5 micrograms/kg) or saline administered as intraperitoneal injections every 8 hours. Tumor area was measured twice weekly until mice were sacrificed (day 28), when tumor and normal pancreas were removed, weighed, and assayed for DNA and protein content. Both mRNAs and peptides of gastrin and chromogranin A were present in PT tumors. Bombesin significantly stimulated growth of PT tumors from day 18 until mice were sacrificed (day 28). As expected, bombesin stimulated pancreatic growth. We have demonstrated for the first time that bombesin is a trophic hormone for gastrinoma. The unique cell line PT contains gastrin and chromogranin A and will be a useful model to define the biologic mechanisms controlling the growth of human gastrinomas.


Family members of patients with sporadic medullary thyroid carcinoma must be screened for hereditary disease. Medullary thyroid carcinoma (MTC), a tumor arising from calcitonin-secreting C cells, appears in either a sporadic nonfamilial or a hereditary form as a component of a multiple endocrine neoplasia syndrome or familial non-multiple endocrine neoplasia MTC. Screening kindred of a patient with familial MTC to detect MTC in the early curable state is standard practice. Opinions conflict about whether it is necessary to screen relatives of patients with apparently nonfamilial MTC to exclude hereditary disease or whether the clinicopathologic features can differentiate between the two forms. Clinically well kindred of a patient with MTC that was histopathologically characteristic of the sporadic type were screened for hereditary disease by measurement of plasma levels of basal and stimulated calcitonin. Three of four immediate relatives tested positive for excessive calcitonin secretion and underwent thyroidectomy. All had C-cell hyperplasia, the premalignant phase of MTC. The patient with apparently sporadic (nonfamilial) MTC was clearly an index case of familial disease. We conclude that clinical presentation and histopathologic examination are not adequate to reliably exclude hereditary MTC. Until genetic markers are readily available to distinguish between sporadic and familial forms, biochemical screening should be done in primary relatives of all patients with newly detected MTC.


Relationships of parathyroid hormone, parathyroid secretory protein, parathyroid hormone messenger RNA, parathyroid secretory protein mRNA, and replication in human parathyroid adenoma and secondary hyperplasia tissues and cultures. The purpose of this study was to clarify the relationships of extractable and secreted parathyroid hormone (PTH) and parathyroid secretory protein (PSP) in human parathyroid tumors to PTH messenger RNA (mRNA), PSP mRNA, and cell replication. In tissue cultures of seven adenomas and five secondary hyperplasias, we found a direct correlation for secreted PTH versus PSP for both adenomas and secondary hyperplasias. Secreted PTH:PSP was elevated for adenomas (11:1) compared to that of secondary hyperplasias (2:1), and adenomas secreted significantly more PTH and PSP than did secondary hyperplasias. In extracts of eight adenomas and six secondary hyperplasias, the ratio of PTH:PSP was unexpectedly low (2:1) and similar for both adenomas and secondary hyperplasias. The ratio of extractable PTH mRNA:PSP mRNA was extremely low for both adenomas (1:7) and for secondary hyperplasias (1:5). Flow cytometry indicated that percent replication was inversely correlated with PTH mRNA and PSP mRNA. Increased PTH secretion by adenomas cannot be attributed to increased biosynthetic capacity because it is less than expected. Hypersecretion of PTH by adenomas and coincident marked reductions in PTH mRNA suggest either a defect in cytoplasmic storage of PTH or impairment of normal posttranslational degradation of PTH. As parathyroid tumor cells increase replication, PTH mRNA is reduced. Possible explanations for this include decreased PTH gene transcription or decreased mRNA half-life.


The effect of cryopreservation on cell viability and hormone secretion in human parathyroid tissue. To explain the decreased success of cryopreserved versus fresh parathyroid autotransplants, we investigated the effect of cryopreservation on parathyroid function. Parathyroid cryopreserved tissue from surgical specimens of 18 patients was analyzed in a comparative fashion with 10 fresh abnormal glands. Cell viability was evaluated by a double-fluorescence technique, and parathyroid hormone secretion was detected from individually dispersed parathyroid cells with the reverse hemolytic plaque assay. The plaque area reflected the amount of parathyroid hormone secreted by each cell, and the percentage of plaque-forming cells represented the number of secreting cells. Feedback regulatory mechanisms remained intact for both fresh and cryopreserved tissue as shown over a wide range of calcium concentrations. The percentage of viable cells from fresh and cryopreserved tissue was always in excess of 88%. No significant difference was noted in the percentage of plaque-forming cells nor the amount of hormone released per individual cell comparing fresh and cryopreserved glands (6 months to 2 years). Specifically, at physiologic calcium concentrations no significant differences existed in the secretory behavior between fresh and cryopreserved tissue. Without showing decreased viability or parathyroid hormone secretion after cryopreservation, the cause of graft failure in cryopreserved tissue still remains unknown.


Role of the oral calcium-loading test with measurement of intact parathyroid hormone in the diagnosis of symptomatic subtle primary hyperparathyroidism. This study was designed to assess the diagnostic value of the oral calcium tolerance test with measurement of intact parathyroid hormone by the immunoradiometric assay (IRMA PTH) in the diagnosis of primary hyperparathyroidism in patients with symptoms who have minimal, intermittent, or no elevation of the levels of total calcium and/or intact PTH. After baseline levels of IRMA PTH and total calcium were measured, an oral calcium load of 1000 mg elemental calcium was administered to 10 patients with hyperparathyroidism and 18 normal control subjects. Total calcium and IRMA PTH levels were measured at 30, 60, and 120 minutes after the oral calcium load was administered. The mean suppression of the baseline level of IRMA PTH in the patients with hyperparathyroidism was 83.7% +/- 6.5% (mean +/- 1 SEM), but the levels of the normal control subjects fell significantly (p < 0.05) lower to 58.8% +/- 3.7% (mean +/- 1 SEM). This study suggests that the oral calcium tolerance test may be a valuable adjunct in confirming the diagnosis of primary hyperparathyroidism in patients with symptoms who have minimal, intermittent, or no elevation of the levels of total calcium and/or IRMA PTH:


Prospective evaluation of the efficacy of technetium 99m sestamibi and iodine 123 radionuclide imaging of abnormal parathyroid glands. Technetium 99m sestamibi is an isonitrile radionuclide imaging agent that, when used with subtraction iodine 123 thyroid scans, has the potential for imaging abnormal parathyroid glands. We prospectively evaluated 20 patients with hyperparathyroidism to study the efficacy of Tc 99m sestamibi and 123I subtraction radionuclide scanning for the imaging of abnormal parathyroid glands. All patients underwent neck exploration and histologic confirmation of all parathyroid glands identified. The solitary adenomas in 11 of 16 patients with primary hyperparathyroidism were localized with sestamibi scans. The scans in four of five patients with diffuse parathyroid hyperplasia showed bilateral localization consistent with enlarged glands. The fifth patient previously underwent a subtotal parathyroidectomy, and a fifth supernumerary gland was localized with the sestamibi scan. Four patients had hyperparathyroidism related to kidney disease. Three of these had bilateral localization of enlarged glands. The fourth patient had undergone two previous operations, and a fifth supernumerary gland was localized with the sestamibi scan. The preliminary data indicate that Tc 99m sestamibi in combination with 123I radionuclide scanning may be useful in the preoperative localization of abnormal parathyroid glands. This technique localized all of the solitary adenomas that were subsequently resected, and in two reoperative cases it identified the remaining solitary gland causing persistent hypercalcemia.


Long-term effects of parathyroid operation on serum calcium and parathyroid hormone values in sporadic primary hyperparathyroidism. This study investigates 410 persons (median age, 67 years) who underwent parathyroid operation for sporadic primary hyperparathyroidism 6 to 32 years (mean, 14.2 years) before 1991. Patient records and operative specimens were scrutinized, the patients answered a questionnaire, and fasting serum samples were analyzed for calcium, albumin, creatinine, and intact parathyroid hormone (PTH) values. After primary parathyroid operations were performed with a conservative surgical approach, persistent and recurrent hypercalcemia were noticed in 3.7% and 1.7% of patients, respectively, whereas 4.7% of patients required vitamin D substitution or had essentially mild hypocalcemia. The PTH values were generally increased in patients with postoperative hyperparathyroidism, low in those with vitamin D substitution, and normal to elevated in the patients with hypocalcemia and in those with postoperative normocalcemia. The mean serum creatinine concentration was just below the upper reference range and correlated strongly with serum PTH value. No significant differences in serum PTH values were present between the normocalcemic patients and matched control patients after operation (n = 107), but the patients who underwent operation exhibited greater variation in the PTH concentration. The results substantiate the efficacy of parathyroid operation in sporadic primary hyperparathyroidism. Biochemical derangements compatible with secondary hyperparathyroidism may evolve during long-term follow-up and contribute to decreases in serum calcium values and increases in serum PTH values of these patients.


Follicular thyroid carcinoma with capsular invasion alone: a nonthreatening malignancy. The study was designed to determine whether invasion of the tumor capsule, in the absence of vascular invasion (VI), was significant in predicting cause-specific mortality in follicular thyroid carcinoma (FTC). Seventy-two patients with FTC were treated by us during 1971 through 1985. In 65 cases the tumors could be classified as either showing capsular invasion (CI) alone (20) or VI, with or without CI, (45). Median follow-up of 45 survivors was 11 years; 12 patients died of FTC. The 10-year occurrence rates for cause-specific mortality and distant metastases were 28% and 19%, respectively, for patients with VI. Comparable rates for the patients with CI were 0% (p = 0.019) and 0% (p = 0.052), respectively. By univariate analysis, higher rates of cause-specific mortality were significantly associated with distant metastases at diagnosis (p < 0.0001), the presence of VI (p = 0.019), and moderate or marked microinvasion (p = 0.019). In stepwise multivariate analyses, only distant metastases at diagnosis had independent prognostic significance (p < 0.0001) in the prediction of cause-specific mortality. In a Cox model, adjusting for distant metastases at diagnosis, the presence of VI was of borderline significance (p = 0.06) in predicting cause-specific mortality. FTC, diagnosed on the basis of CI alone, did not result in either distant metastases or cancer-related death. The dominant determinant of cause-specific mortality was the presence of distant metastases at diagnosis.


Papillary thyroid microcarcinoma: a study of 535 cases observed in a 50-year period. The study aims were to characterize patients with papillary thyroid microcarcinoma and to provide data on outcome after surgical therapy. Five hundred thirty-five patients with papillary microcarcinoma had initial treatment at Mayo Clinic from 1940 to 1989. Follow-up extended to 48 years. Median follow-up time for 400 survivors was 16 years. Recurrence and mortality details were derived from a computerized cancer database. Median tumor size was 8 mm. Ninety-nine percent of tumors were histologic grade 1; 98% were not locally invasive. Thirty-two percent of patients had nodal metastases at examination. TNM stages were I in 485 patients (91%), III in 49 patients (9%), and IV in one patient (0.2%). Ninety-one percent of patients underwent bilateral lobar resection. Tumor resection was incomplete in three cases (0.6%). Radioiodine remnant ablation was performed in 55 patients (10%). All-causes survival did not differ from expected; two patients (0.4%) died of papillary microcarcinoma. Twenty-year tumor recurrence rate was 6%. Higher recurrence rates were seen either with node-positive patients (p < 0.0001) or after unilateral lobectomy (p < 0.0001). Recurrence rates did not appear to be significantly altered by total thyroidectomy (p = 0.44) or radioiodine remnant ablation in node-positive patients (p = 0.99). These results reaffirm that papillary microcarcinoma has an excellent prognosis if managed initially by bilateral lobar resection. Routine radioiodine remnant ablation is not indicated.


Completion thyroidectomy: a critical appraisal. Completion thyroidectomy can most accurately be described as reexploration of the neck to remove the contralateral thyroid lobe. This procedure has commonly been performed when the histopathologic condition of the ipsilateral thyroid lobe reveals papillary or follicular carcinoma of the thyroid. Because of a definitely increased risk of complications with completion thyroidectomy, avoiding its routine use is important. The purpose of this paper is to define the specific indications for completion thyroidectomy. Over the past 9 years, we have performed 400 thyroidectomies; the patients ranged in age from 18 to 88 years. Although we have routinely used preoperative needle biopsy and intraoperative frozen section, decisions regarding the extent of thyroidectomy have been based on the gross findings at operation, taking into consideration such prognostic factors as patient age, tumor grade and size, the presence of extracapsular spread or distant metastasis, and associated risk factors. The minimal procedure for solitary thyroid nodule has been lobectomy with isthmusectomy. If the contralateral lobe is grossly normal, lobectomy with isthmusectomy has also been the maximal operation in most of patients. Very few specific indications exist for removal of the opposite lobe. Only three patients underwent completion thyroidectomy. All three patients had aggressive follicular carcinoma requiring radioactive iodine ablation, and all were referred after the initial surgery. We have not performed completion thyroidectomy on any of the patients on whom we initially operated. The most common indication considered for completion thyroidectomy is a frozen section diagnosis of a benign follicular adenoma that is subsequently changed on permanent pathologic condition to follicular carcinoma based on the presence of capsular and/or vascular invasion. However, if minimal invasion has occurred, no difference exists in survival related to the extent of the thyroidectomy. Local recurrence in the contralateral lobe occurs in less than 10% of the time. Because completion thyroidectomy carries more risks, it should be avoided in most patients when possible. The definitive decision should be made during the initial operation based on gross findings, prognostic factors, and frozen section, and this plan should only be changed to mandate completion thyroidectomy in select circumstances.


Addition of nuclear DNA content to the AMES risk-group classification for papillary thyroid cancer. The purpose of this study was to prospectively assess whether nuclear DNA content added prognostic value to existing risk factors in patients with papillary thyroid cancer. Nuclear DNA content was measured both on the fine needle aspiration material and the surgical specimen in 73 patients with primary or recurrent papillary thyroid cancer. We modified the existing age of patient, presence of distant metastases, extent and size of the tumor (AMES) risk-group classification to include DNA ploidy with AMES (DAMES). Patients with euploid tumors that were AMES low risk were considered to be DAMES low risk; patients with euploid tumors that were AMES high risk became intermediate risk, and patients with aneuploid tumors that were AMES high risk became DAMES high risk. Forty-eight patients were in the DAMES low-risk group. Recurrences and/or distant metastases developed in only four (8%) of these patients. Twenty-two patients were in the DAMES intermediate-risk group. Twelve (55%) of the intermediate-risk group had residual, recurrent, or distant metastatic disease, with one death from cancer at 120 months. Three patients were in the DAMES high-risk group. Distant metastases developed in all three patients, who died within 24 months from thyroid cancer. A statistically significant difference existed in the development of recurrence/metastases or death from cancer in the DAMES high-risk group compared with the other risk groups combined. Nuclear DNA content adds prognostic value to the existing AMES risk-group classification. Because DNA analysis on fine needle aspiration correlated well with the surgical specimen DNA analysis, this modified classification can be used perioperatively to further individualize the treatment of patients with papillary thyroid cancer.


Percutaneous intranodular ethanol injection for treatment of autonomously functioning thyroid nodules. The aim of the study is the assessment of percutaneous intranodular ethanol injection (PNEI) as an alternative therapeutic procedure to classic surgery and radioiodine administration in autonomously functioning thyroid nodule treatment. Thirty-seven patients with hot nodules (18 pretoxic and 19 toxic) have been treated by means of PNEI under ultrasonographic guide. Ninety-five percent ethanol in a mean dose of 25 ml has been used. Nearly 80% of the patients showed normalization of thyroid-stimulating hormone levels and a complete recovery of extranodular tissue at scintiscan. All nodules decreased strikingly in size, many becoming undetectable. Mild and transient side effects were seen in 9% of the patients. PNEI seems to be a feasible procedure on outpatients. It is safe when performed by a well-trained staff using ultrasonographic control. It may be carried out at any age and in patients at risk for surgery. PNEI can be considered a useful alternative to surgery and radioiodine administration in all autonomously functioning thyroid nodules and particularly in pretoxic nodules.


Treatment of toxic solitary thyroid nodules: surgery versus radioactive iodine. Because of controversy about the correct treatment of toxic solitary thyroid nodules, we reviewed our experience. We retrospectively studied 32 patients (24 women and 8 men) with solitary toxic thyroid nodules who were treated at our institution (1970 to 1985). Median values were as follows: age of patients at initial treatment, 67.6 years (range, 18.9 to 86.2 years); follow-up, 3.8 years; largest diameter of nodules, 3.3 cm (range, 1.5 to 6 cm); and 131I uptake at 24 hours, 31% (range, 7% to 54%). Nine patients had surgical treatment: subtotal thyroid lobectomy in six patients and subtotal thyroidectomy in three patients. Hypothyroidism developed in two of these nine patients (22%) 9 months after operation. No surgical complications occurred. No surgically treated patient had nodule recurrence or required re-treatment. Twenty-three patients were treated with radioactive iodine (median dose, 29.1 mCi; range, 19.7 to 100 mCi). Two of them were re-treated: one patient underwent thyroid lobectomy because of concern about the nodule, and one patient was re-treated with radioactive iodine because of persistent toxicity. Hypothyroidism was detected in eight of the 23 patients (35%) treated with radioactive iodine after treatment. Of the 16 patients treated with radioactive iodine with at least 1 year follow-up and no re-treatment, nine (56.3%) have had complete regression of the nodule. Surgical excision of solitary toxic thyroid nodules would appear to be the treatment of choice.


An eleven-year experience with adrenocortical carcinoma. Key issues in the treatment of adrenocortical carcinoma are the value of adjuvant therapy, the value of reoperation, and the search for effective chemotherapeutic agents. The present series was reviewed to evaluate these issues. We present a retrospective series of 73 patients with adrenocortical carcinoma treated at a single institution. Twenty patients had carcinomas that were unresectable, and 53 patients underwent complete resections. Ten patients received adjuvant therapy (mitotane, seven patients; radiation, three patients). Forty-five (85%) patients had recurrence, including all who received adjuvant therapy. Mean disease-free intervals for those who did and did not receive adjuvant therapy were equivalent at 2.4 years. Nineteen patients with recurrent disease received chemotherapy, and 26 patients underwent 51 reoperations to resect recurrent and metastatic disease. The overall 5-year survival rate, which was 35%, was 47% for patients with complete resection. Stage and resectability were prognostic factors. Mean survival time for patients with recurrent disease treated medically was 19 months compared with 56 months for patients who underwent reoperation. Mitotane had a 24% partial response rate. Other chemotherapeutic agents were ineffective. We conclude that an aggressive surgical approach to recurrent and metastatic disease should be adopted and that patients should be resected free of disease whenever possible. Currently no effective chemotherapy exists, and the value of adjuvant therapy remains unproved.


Adrenocortical carcinoma in surgically treated patients: a retrospective study on 156 cases by the French Association of Endocrine Surgery. Because of the rarity of adrenocortical carcinoma, survival rates and prognosis for patients who have undergone operation are not well known. The purpose of the French Association of Endocrine Surgery was to evaluate these factors in all patients treated during a 12-year period by its members. One hundred fifty-six patients (95 women, 61 men) with a mean age of 47 years were included. Functional symptoms were found in 52% of patients, and hormonal studies revealed secreting tumors in 62% of cases. Ninety-four percent of the patients underwent resection of the adrenal tumor, and 20% of them had extensive resection because of invasive cancers. Complete resection was achieved in 127 patients (81%) and incomplete resection in 29 patients. Mean tumor weight was 714 gm (range, 12 to 4750 gm), and the mean diameter was 12 cm (range, 3 to 30 cm). The results of the tumor staging were stage I, eight patients (5%); stage II (local disease), 75 patients (48%); stage III (locoregional disease), 39 patients (25%); and stage IV (metastases), 34 patients (22%). The 5-year actuarial survival rates were 34% overall, 42% in curative group, 53% in local cancer group, 24% in regional disease group, and 27% in the reoperated group. One-year actuarial survival rate of the palliative group was 9% (median survival, 6 months). Multivariate analysis showed that better prognosis occurred in patients younger than 35 years of age (p = 0.01) and in patients with androgen-secreting tumors, precursor-secreting tumors, or nonsecreting tumors (p = 0.003). Mitotane improved the survival rate only in patients with metastases who received it after operation (vs non-mitotane-treated patients [p < 0.05]). In this study age, extent of disease, aspect of the surgical resection, and type of hormonal secretion influenced survival.


Risk factors associated with postoperative persistent hypertension in patients with primary aldosteronism. Unilateral adrenalectomy was performed in 63 patients with primary aldosteronism. During a mean follow-up time of 4.1 years, none of the patients showed recurrence of hyperaldosteronism. However, 24 patients (38%) had persistent hypertension. The purpose of this study was to determine factors responsible for postoperative persistent hypertension. A stepwise multivariate logistic regression analysis was performed to assess the combined predictive effects of the clinicopathologic variables. Age, sex, and pathologic findings were the best predictive factors of postoperative persistent hypertension. For a patient aged 50 years or more, the odds of persisting hypertension are 10.6:1, compared with those of a patient under 40 years of age. A male patient appears to have a greater chance of hypertension than a female patient; the odds ratio is 5.9:1. Persistent hypertension develops in patients with multiple adenomas or with an adenoma associated with macronodules more frequently than in those patients with a solitary adenoma; the odds ratio is 8.1. This study suggests that early surgical intervention at a younger age results in a more favorable outcome for patients with primary aldosteronism. The presence of macronodules in association with an adenoma is a cautious predictor of persistent hypertension after adrenalectomy.


Acupuncture and occlusal splint therapy in the treatment of craniomandibular disorders. Part I. A comparative study. One hundred and ten patients, 23 males and 87 females, participated in a comparative study of the effect of acupuncture and occlusal splint therapy. All the patients exhibited signs and symptoms of craniomandibular disorders (CMD) and had had pain for more than six months. The participants were randomly assigned to three groups; acupuncture treatment, occlusal splint therapy or control. The patients were evaluated before and immediately after treatment/control time. Ten different subjective and/or clinical assessment variables were used in the evaluation of the treatment effects. Both acupuncture and occlusal splint therapy reduced the symptoms as compared with the control group in which the symptoms remained essentially unchanged. In this short-term study, acupuncture gave better subjective results (p < 0.001) than the occlusal splint therapy.


Dental caries in a group of 15 to 16-year-olds from Göteborg. Part I. 301 adolescents aged 15 to 16 years (158 girls and 143 boys) were examined for caries under standardized conditions during the fall and spring terms of 1987/88. Clinical examinations, performed by two calibrated examiners were supplemented with posterior bite-wing radiographs which were assessed by one of the examiners. The mean DFT and DFS scores (incipient lesions included) were 9.8 and 19.4, respectively. The mean DFS score (dentin lesions+restorations) was 6.4. On average 1.9 surfaces had frank cavities or recurrent lesions and 13 surfaces had incipient lesions. Occlusal surfaces contributed 75%, approximal 21% and bucco-linqual 4% to the manifest component of the DFS score (4.8, 1.4 and 0.2 surfaces, respectively). 3% of the incipient lesions were found occlusally, 51% approximally and 46% bucco-linqually (0.4, 6.6 and 5.9 surfaces, respectively). Only 3% of the participants were completely free from caries, whereas 9% had no dentin lesions or restorations. 15% of the subjects with the highest caries prevalence averaged 15.8 dentin lesions or restorations. A tendency towards polarization of low and high caries prevalence groups was observed. Totally 91% of the individuals had occlusal caries, 82% approximal and 76% bucco-lingual, whereas dentin lesions or restorations had 88%, 42% and 14%, respectively.


Pain control after third molar surgery--a comparative study of ibuprofen (Ibumetin) and a paracetamol/codeine combination (Citodon). Two analgesics commonly used in oral surgery, ibuprofen (Ibumetin) and a paracetamol/codeine combination (Citodon) have been compared in a single-blind multi-centre trial after third molar surgery. The study comprised 120 patients, 60 in each treatment group. The profiles of postoperative pain in the two groups were similar from the first postoperative day, but Ibumetin was better pain reliever on the day of surgery. The profiles of postoperative swelling and trismus had the same general course, but patients taking Ibumetin reported lower scores for these variables during the whole postoperative period. Citodon induced significantly more side-effects than Ibumetin.


Root development of the lower third molar and its relation to chronological age. Methods based on radiological, distinguishable stages of tooth formation can be used to estimate chronological age in young persons. The best precision and accuracy of these methods of age estimation is obtained when many teeth are under development and when the individual growth rate is rapid. That is during early years-in childhood. After an age of about 14 years it becomes more difficult since all permanent teeth but the wisdom teeth have completed their development and only these remain to be used for age estimation. The aim of this study was to examine the radiological development of the root of the mandibular third molar and to explore its usefulness in age estimation. Also the differences between two independent observers were studied. The observers classified the development of the mandibular third molars, as seen in a panoramic radiograph, into seven defined stages. The two observers agreed in about 84% of the cases in their registration of the different stages, but a significant difference was found between the observers. The mineralisation of the third molar's root was found to start at the age of 15 years and the root was fully formed at about 20 years. Some minor differences were found between sexes in the time sequence of the mineralisation. The study also shows that there is a rather low precision in the age estimation with the method used. In general, a standard deviation of about 1 to 2 years was found around the mean age of the different developmental stages.


A clinical evaluation of adhesively luted ceramic inlays. A two year follow-up study. Fired porcelain inlays were cemented in class II cavities with either a dual cured composite or a glass ionomer luting cement. Clinically evaluation according to modified USPHS criteria was done at baseline and after 6, 12 and 24 months. Inlays bonded with the composite resin showed a 2% failure rate, while 15% of the inlays cemented with the glass ionomer were lost or fractured during the evaluation period. The failures were in most cases due to an adhesive bond failure at the cement-porcelain interface.


[Ceramic brackets].

[Ceramic brackets]. Because of the many drawbacks of the hard and brittle material, ceramic brackets should not be used uncritically for orthodontic treatments. If ceramic brackets are used, the following guidelines should be observed: 1. If large and complicated tooth movements are involved, conventional bracket systems should be considered. 2. Occlusion on ceramic brackets is to be avoided. 3. Sharp instruments should be used with extreme care to avoid scratching the ceramic surface. Metal ligatures must not be used. 4. The length of the treatment is extended, probably because of the increased friction. 5. The problems connected with removing the brackets have not yet been solved. Be particularly careful of weakened teeth. 6. Esthetically, ceramic brackets function satisfactorily, but transparent elastic ligatures do not. They rapidly become discoloured and need frequent replacement. Nor are there as yet any "invisible arch wires", apart from some few, extremely flexible "white" arch wires. The ceramic bracket has no doubt come to stay, but there have been many difficulties in the "running-in" period, and the problems are far from solved yet. New ceramic brackets are coming onto the market all the time, and only future clinical studies can show whether they will become a genuine alternative to the conventional bracket.


[Dislocation of mandibular condyle into middle cranial fossa]. A case of dislocation of the mandibular condyle into the middle cranial fossa is presented. The patient was a 8-year-old girl. Immediate conservative reposition was performed successfully with an intermaxillary fixation for two weeks. Two years after the accident her dental occlusion had remained stable, although there was a slight limitation in opening. Based on the present case and previous case reports it is concluded that early diagnosis and treatment is important. Manual reduction and fixation should be the first choice of treatment. The risk of intracranial complications necessitates a close cooperation with a neurosurgeon. Follow-up studies have revealed that most of the patients develop laterognatism and/or limited movements of the mandible.


[Bilateral eminectomy in the surgical management of recurrent jaw luxation]. The different types of luxations in the temporomandibular joint and their management are discussed. The bilateral eminectomia a.m. Myrhaug is described, and the results from our Department are presented. Seven patients have been operated, and all are relieved of their disease and free from pain. The patients are happy with the operations and there have been no postoperative complications. All the patients would recommend this type of operation to others in a similar situation.


[The clinico-immunological characteristics of central nervous system involvement in systemic lupus erythematosus: the relationship with antibodies to cardiolipin]. As many as 30 patients suffering from systemic lupus erythematosus (SLE) with the clinical signs of central nervous system derangement were examined. The mean age of the patients was 31.1 years. Using EIA, antibodies against cardiolipin (a-CL) were detected in 21 patients (70%). A-CL were revealed in all the patients with cerebral circulation impairment (CCI), choreic hyperkinesis, and convulsive syndrome. A-CL were discovered in 12 out of 18 SLE patients suffering from migraine-like headaches and in 4 out of 5 patients with mental disorders. Antibodies reacting with cardiolipin were mostly represented by the IgM isotype (80%) whereas a-CL-IgG were only identified in 13% of the patients, being associated in all the cases with a-CL-IgM. The high level of a-CL-IgG in blood serum was recorded in patients with the gravest patterns of nervous system derangement: CCI, occlusion of the retinal artery, psycho-organic and convulsive syndromes. All these patients demonstrated generalized reticular livedo. The high levels of a-CL-IgM were observed in SLE patients with choreic hyperkinesis and migraine-like headaches. Thus, the studies made it possible to trace the relationship between the development of certain neurological disorders (CCI, chorea, convulsive syndrome) in SLE patients and a-CL.


[The use of Capoten in systemic scleroderma]. Experience gained with the use of captopril has been summarized in 5 patients with sclerodermic renal crisis (true sclerodermic kidney) as well as the results of the double blind clinical trial of captopril in 16 patients with Raynaud's syndrome. Captopril given for a long time in the dose 75-150 mg to the patients with true sclerodermic kidney turned out effective which showed up by a decline and stabilization of arterial pressure, decrease of the intensity of azotemia and headaches, and stabilization of renal function. No convincing data have been obtained, that may confirm a beneficial effect of captopril on Raynaud's syndrome. The drug was applied in a dose of 37.5 mg for 2 weeks.


[Spondylarthritis ankylopoietica and HLA-B27]. There is a strict association between HLA-B27 and a group of spondylarthropathies, especially with ankylosing spondylarthritis (AS). The causes of the association remain obscure, different hypotheses are regarded. There is an interaction between B27 and bacteria. However, the etiological and pathogenetic roles played by any of them in AS cannot be regarded as proved. B27 is an important genetic factor in the disease expression. It is implicated in the pathogenesis, being undoubtedly a risk factor. At the same time it cannot be excluded that B27 is only one of the genes, predisposed to the disease. From the practical standpoint, it is important that the I degree kinship relatives of AS patients, males in particular, having HLA-B27 may be subjected to prophylactic medical examinations.


[Immunological disorders in different clinical variants of rheumatoid arthritis]. The authors present the current data on the disorders of immune functions in patients suffering from rheumatoid arthritis (RA). Provide evidence for the pathogenetic heterogeneity of the known clinical patterns of RA, mainly seronegative and seropositive varieties, with special reference to the differences in the lowering of the activity of nonspecific T suppressors, to the influence of the factor of necrosis of alpha-tumor and alpha- and beta-interferons on B lymphocyte proliferation, and to the effects of synovial exudate from seropositive and seronegative patients. Demonstrate the results of integral estimation of the disorders of several characteristics of the immune system in RA patients with the use of the image recognition program. It is concluded that the clinical polymorphism of RA is specified by the pathogenetic heterogeneity of the disease based on varieties of combined normal and altered functions of different components of the immune system.


[The biochemical heterogeneity of rheumatoid arthritis]. The content of cyclic nucleotides (cAMP and cGMP) in plasma (or blood), synovial fluid and neutrophils was measured in 151 patients suffering from rheumatoid arthritis (RA) as was the content of prostaglandins (E2 and F2 alpha), ACTH, hydrocortisone, antioxidant system enzymes (superoxide dismutase and catalase). Part of the patients were examined over time. Relative stability of certain characteristics (the content of hydrocortisone, neuropeptides, superoxide dismutase, and so forth) was established throughout a long time, irrespective of the process activity or treatment provided. It is concluded that every RA patient has a "weak" biochemical component of his own, reflecting the activity or power of one or another regulatory system.


[Changes in the production of monokines and prostaglandin E2 by the peripheral blood monocytes in patients with different clinico-immunological variants of rheumatoid arthritis]. As many as 39 patients aged 16-70 years with rheumatoid arthritis (RA) lasting 3 months to 20 years were examined. The diagnostic titers of rheumatoid factor were discovered in 23 patients. The control group was made up of 26 healthy subjects (donors). The activity of IL-1 in supernatants of peripheral blood monocytes (PBM) was measured by bioassay resting on co-stimulation of mouse thymocytes; quantitative determination of tumor necrosis factor-alpha (TNF-alpha) was made by ELISA, PGE2 was determined by RIA. As compared to the controls, the RA patients manifested an increase of the production of IL-1 beta, TNF-alpha and PGE2 of PBM, which rose with the disease activity. The RA patients demonstrated direct correlations between the level of IL-1 beta, TNF-alpha and PGE2 in supernatants of PBM, whereas the donors showed up a negative correlation between IL-1 beta activity and PGE2.


[The prediction of thrombosis development in patients with systemic lupus erythematosus: the role of antibodies to cardiolipin]. In patients with systemic lupus erythematosus (SLE), the synthesis of antibodies to cardiolipin (A-CL) is associated with the development of venous and arterial thromboses localized in minor and middle-sized vessels, in the venous system and capillaries. The determination of various A-CL isotypes may be used to predict thromboses in SLE patients. Overall 210 patients (185 women and 25 men) with a verified diagnosis of SLE were examined. The patients were not screened in accordance with some or other clinical signs of the antiphospholipid syndrome. The control group comprised 100 healthy subjects (donors). The IgG, IgA and IgM isotypes of A-CL were determined by ELISA. Sera of SLE patients showed an increase of the concentration of A-CL of both certain isotypes and their potential combinations. Among A-CL-positive patients, the IgG isotype of A-CL was detected in 75% of cases, the IgM isotype of A-CL in 61%, and the IgA isotype of A-CL in 36% of cases. Thrombotic complications were recorded in 19% of patients. They were induced by hyperproduction of the three combinations of the A-CL isotypes: A-CL IgM, IgM+IgA, and IgG+IgA+IgM. Patients whose sera contained A-CL of all three types at a time were most prone to thrombotic complications. It has turned out that the percentage of SLE patients with thromboses was higher than that of SLE patients without thromboses, starting from the definite A-CL concentration (21 GPL).(ABSTRACT TRUNCATED AT 250 WORDS)


[A comparative evaluation of combined immunocorrective therapy in rheumatoid arthritis with systemic manifestations (joint Soviet-Polish research)]. Thirty-two patients with rheumatoid arthritis were included in the trial. Each of them was assigned to one of the 4 groups comparable by the main features. Each group entered 8 patients. Group 1 patients underwent hemosorption weekly for 3 weeks. After the second procedure cyclophosphamide was added at a single IV dose 1000 mg. After the third procedure the treatment was continued with methotrexate (7.5 mg, weekly). Group 2 began the treatment with methotrexate (7.5 mg, weekly). Group 3 received cyclophosphamide 200 mg IV twice a week 6 times and then 200 mg weekly orally till a total dose of 2 g. Group 4 received azathioprine in a daily dose 100 mg. The treatment with nonsteroidal antirheumatic drugs and corticosteroids was continued unchanged. After 6 months we did not see significant differences between the 4 groups.


[The efficacy of basic therapy in rheumatoid arthritis with methotrexate]. Overall 25 patients with rheumatoid arthritis received methotrexate as basic therapy in a weekly dose of 7.5 mg. The patients were followed up for a year. The control examinations were carried out every three months. The therapeutic effect was evaluated from the dynamics of 10 clinical and laboratory parameters. The efficacy of methotrexate treatment provided for a year turned out as follows: significant improvement was attained in 11 patients, improvement was recorded in 9; no changes were demonstrated by 5 patients. Thus, the positive effect was attained in 20 patients (80%). A clinical remission was recorded in 4 patients. Small doses of methotrexate were tolerated well. During one year, the drug was discontinued in none of the patients. Mild side effects were noticed in 11 patients. The temporary drug withdrawal made it possible to continue treating those patients. The majority of the humoral immunity tests showed positive dynamics. As for the titers of rheumatoid factors, such regularity could not be traced.


[The possibilities for a modifying influence of basic therapy on the long-term course of rheumatoid arthritis]. Analysis was made of the results of basic therapy carried out for 10-15 years in 71 patients suffering from rheumatoid arthritis (RA) bearing in mind the systematic nature of the treatment. The study included patients with the progressive disease variety and the onset of observation instituted within the first 5 years of RA. It is shown that only basic therapy carried out for many years and practically continuously during the observation period made it possible to control the disease. As a result of such treatment policy, 50% of the patients manifested for a long time (6-10 years) a pronounced decrease or complete suppression of RA activity followed by remission, which was accompanied by retardation and the ceasing of the progression of x-ray alterations and functional insufficiency of the joints. Nonsystematic basic treatment did not exert any material effect on RA. The results of such therapy in patients with the RA standing 10-20 years did not differ from those without the use of the basic drugs.


[Pulse therapy with methylprednisolone and cyclophosphamide in systemic juvenile rheumatoid arthritis: the results of an open, parallel, controlled, randomized, 12-month study]. The treatment for systemic JRA is among actual problems of pediatric rheumatology. To evaluate the effectiveness of pulse therapy (PT) with methylprednisolone 25-30 mg/kg/day for 3 consecutive days combined with cyclophosphamide 0.4-0.5 g/sq. m body surface area (BSA) on the 3rd day, repeated quarterly for 12 months, 30 patients with systemic JRA were randomized into 3 groups: 1--those with disease duration (DD) less than 2 years receiving PT (n = 13), 2--with DD 2 years and more (n = 8) receiving PT, and 3--with DD less than 2 years receiving no PT. Children in all 3 groups received concomitant medication (one of nonsteroidal anti-inflammatory drugs, methotrexate 10 mg/sq. m BSA/week and oral steroids). A rapid and significant improvement, according to systemic and articular manifestations as well as laboratory indices occurred in the 1st group, in most of the measured parameters exceeded effects in the other two groups and gave the opportunity to avoid the administration of oral steroids or to give the lesser initial dose. Side effects were minor and completely reversible.


[The immunomodulating action of extracorporeal treatment methods and the late effect from their use in patients with rheumatoid arthritis]. Unlike hemocarboperfusion (HCP), plasmapheresis (PA) produces a long-term effect in the treatment of serious cases of rheumatoid arthritis. This explains why the rebound syndrome occurs in PA two times less frequently. The analysis of the immunomodifying action of both the treatments and comparison of their efficacy suggest the conclusion that long-term and complete remissions are associated with the immunosuppressive effects, while the development of exacerbations accompanies the immunomodifying effect. HCP stimulates the immune system, while PA can induce both stimulation and suppression. Therefore, HCP can be used as an adjuvant treatment of highly active rheumatoid arthritis before the basic therapy. In PA immunosuppressive effect, it may be used as an original treatment method.


[The preliminary results of using tramal in rheumatoid arthritis patients]. Patients suffering from active rheumatoid arthritis (RA) were examined for the analgesic effect of tramal. All the patients were administered basic therapy and nonsteroidal anti-inflammatory drugs. Tramal produced a beneficial effect in 79% of the patients. The stable analgesic effect ensued on days 3-5 since the onset of continuous treatment. Provided the drug was administered for a short period of time (not more than 14 days), addiction to tramal was not recorded. Only 11% of the patients demonstrated tramal-induced side effects (drowsiness, dizziness, skin itch), seen in cases where the daily dose exceeded 300 mg.


[Cartilage-protective preparations in the therapy of osteoarthrosis]. Based on an analysis of the current data on the pathogenesis of osteoarthrosis, the authors provide evidence for the importance of chondroprotective therapy. Present comparative experimental and clinical (tentative) data on the efficacy of chondroprotective drugs.


[The clinico-immunological subtypes of systemic lupus erythematosus]. Based on clinico-immunologic studies subtypes of systemic lupus erythematosus (SLE) were distinguished. The ANF-R++H-DNA-CH50 variant determines acute onset of SLE with renal injury in the form of diffuse glomerulonephritis. The ANF-Sp-RNP-RF mirrors the development of Raynaud's syndrome, Sjögren's syndrome, polymyositis, pneumosclerosis and myocarditis. The ANF-Sp-Ro-RF variant is associated with skin derangement in the form of discoid foci, anular, papulosquamous eruption, vitiligo, hyperpigmentation, and cerebrovasculitis. The Ro-anti-Po, La-anti-La system is related to the idea of SLE, seronegative in accordance with ANF, when rat liver sections are used as a substrate in immunofluorescence.


[Factors that determine the high blood viscosity syndrome in rheumatoid arthritis patients]. High blood viscosity is a syndrome that may be attributed to a group of the most important disorders of microcirculation under different pathological conditions of the body. The given syndrome manifests itself by disorders of red blood cell deformability (RBCD), high plasma and whole blood viscosity. 32 patients with a verified diagnosis of rheumatoid arthritis (RA) were examined, showing varying activity and systemic manifestations. There was a significant decrease of RBCD from 82.0 + 4.5% in patients with grade I activity to 33.0 + 15.0% in patients with grade III activity (p < 0.01). At the same time plasma viscosity remained practically unchanged. Whole blood viscosity rose with RA activity enhancement: in grade I, it was 1.87 + 0.60 relative units, in grade II, it was 2.80 + 0.80 relative units, in grade III, it constituted 5.30 + 3.70 relative units (p < 0.02). It is assumed that RBCD disturbance is one of the most leading signs in the development of high blood viscosity in RA patients.


[The use of taktivin for modulating the functional activity of the neutrophilic granulocytes in patients with systemic lupus erythematosus]. The dynamics of the synthesis of active oxygen forms by neutrophilic granulocytes was studied and compared in patients with systemic lupus erythematosus (SLE) given conventional therapy (n = 14) and combined therapy with the use of tactivin (n = 17). Evaluation of spontaneous fluorescence of neutrophils (FN) and of that induced by suspension of the killed Staphylococcus culture revealed an increase of the latter one after tactivin treatment, which was accompanied by the regression of articular and cutaneous syndromes and trophic disorders. It has been discovered that the dynamics of FN in the treatment with the use of tactivin was dependent on the initial characteristics of the synthesis of active oxygen forms.


[The serum neopterin level in acute rheumatic fever]. Acute rheumatic fever (ARF) is a systemic inflammatory disease etiologically related to infection with group A streptococcus characterized by a broad spectrum of disorders of cellular and humoral immunity. To estimate the activity of the immunopathological process and to forecast myocardial derangement in ARF patients, measurements were made of neopterin in the serum of ARF patients. Nine men with ARF serving in the armed forces were examined. The control group comprised 24 donors. The reference group included 13 patients with dilated cardiomyopathy and 14 with chronic myocarditis. The mean level of neopterin in ARF patients was equal to 14.5 +/- 12.2 nM/l and was significantly higher than in the donors (5.0 +/- 2.0 nM/l). In patients with dilated cardiomyopathy and chronic myocarditis, it was 9 +/- 6 and 16 +/- 11 nM/l, respectively. On more careful clinical analysis the highest level of neopterin was recorded in 3 patients with impairment of the valvular apparatus of the heart. That level was observable during the whole period of the follow-up of the patients. In other patients, no impairment of the valves was detected, whereas the concentration of neopterin fell to normal. Therefore, the rise of the level of neopterin was described for the first time in patients with ARF. Besides, a relationship was found between the high level of neopterin and impairment of the valvular apparatus of the heart.


[The importance of an early stress test in patients with myocardial infarct and heart failure in the acute period of the disease]. The mechanisms of acute myocardial infarction depend on the site of myocardial infarction (MI). In anterior MI, the main factor is a large area of injury; in inferior MI, of importance is dysfunction of the papillary muscles and multiple lesions of the coronary artery in addition to the above factor. The site, the area of injury and the status of the coronary bed influence the rate, character and prognostic value of early load test criteria and contractile function of the left ventricle. In anterior MI, elevation of the ST segment is the most frequent criterion; in inferior MI, its depression. Their combination with other criteria for test discontinuation point to multiple lesions of the coronary artery. In patients with anterior MI, the ejection fraction of the left ventricle amounting to 40%, inadequate growth of AP, anginous pain and the T dominant elevation of the ST segment are unfavourable predictors, allowing the patients to be differentiated in accordance with the risk of postinfarction complications.


[The results of a retrospective examination of patients with acute rheumatic fever]. The authors describe the results obtained during retrospective examinations of 45 subjects who suffered from acute rheumatic fever 10-14 years before. Of these, 19 subjects were treated with prednisolone in the acute disease period, 16 with indomethacin, and 8 subjects with voltaren. The examinations were mostly randomized (30 subjects); no differences in the anti-inflammatory effect were discovered. Heart disease was found in 9 persons (20%). Of these, 6 were treated with prednisolone, 2 with indomethacin, and 1 with voltaren. The disease relapses were recorded in 4 of them, the signs of valvulitis in the past were shown only by 2 persons (echocardiographically). 12 persons (27%) had mitral valve prolapse which had not been diagnosed on the first admission to the hospital, with any clinical signs of hypermotility lacking. In 18 persons (40%) having no valve lesions (disease, prolapse), an x-ray examination revealed a slight increase of the heart size, estimated as a manifestation of postmyocardial cardiosclerosis. Thus, it has been shown that modern anti-inflammatory therapy does not prevent the development of heart disease. Apparently, its onset is related to specific proneness in some of the patients.


[The results of a clinico-serological examination of 60 patients with Lyme disease]. Clinical and serological examinations were carried out in 60 patients with Lyme disease. The diagnosis was established on the basis of the disease marker--tick-borne migrating erythema and serological data obtained with the use of indirect immunofluorescence and Western blot. The spectrum of clinical manifestations and the rate of different clinical syndromes are described and compared with the data by this country and foreign authors. It is shown that Borrelia infection is capable of imitating rheumatic diseases.


A specific immunologic assay for functional plasminogen activator inhibitor 1 in plasma--standardized measurements of the inhibitor and related parameters in patients with venous thromboembolic disease. A new assay for functional plasminogen activator inhibitor 1 (PAI-1) in plasma was developed. The assay is based on the quantitative conversion of PAI-1 to urokinase-type plasminogen activator (u-PA)-PAI-1 complex the concentration of which is then determined by an ELISA employing monoclonal anti-PAI-1 as catching antibody and monoclonal anti-u-PA as detecting antibody. The assay exhibits high sensitivity, specificity, accuracy, and precision. The level of functional PAI-1, tissue-type plasminogen activator (t-PA) activity and t-PA-PAI-1 complex was measured in normal subjects and in patients with venous thromboembolism in a silent phase. Blood collection procedures and calibration of the respective assays were rigorously standardized. It was found that the patients had a decreased fibrinolytic capacity. This could be ascribed to high plasma levels of PAI-1. The release of t-PA during venous occlusion of an arm for 10 min expressed as the increase in t-PA + t-PA-PAI-1 complex exhibited great variation and no significant difference could be demonstrated between the patients with a thrombotic tendency and the normal subjects.


Prolonged bleeding time in patients with lupus anticoagulant. Platelet adhesion to collagen under flow conditions was studied in 18 patients with lupus anticoagulant, seven of which showed a prolonged bleeding time in the presence of a normal platelet count. The effect of patient plasma, IgG and purified anticardiolipin antibodies on platelet adhesion was also examined. We found a significant reduction of platelet adhesion in patients with lupus anticoagulant, which was more evident in patients with prolonged bleeding time. This platelet adhesion defect could be attributed to a plasma factor. In fact, patients' platelets regained normal adhesion when mixed with normal plasma, whereas controls' platelets showed abnormal adhesion in the presence of patient plasma. A causative role of antiphospholipid antibodies was demonstrated in experiments using purified immunoglobulins and anticardiolipin antibodies.


Comparative arterial antithrombotic activity of clopidogrel and acetyl salicylic acid in the pig. We investigated the comparative antithrombotic properties of clopidogrel, an analogue of ticlopidine, and aspirin, using the Folts' model on femoral arteries in 22 pigs. On each animal, clopidogrel or aspirin were used to treat the thrombotic process on the left femoral artery and to prevent this process on the right femoral artery. Sequentially: an injury and stenosis were carried out on the left femoral artery; the thrombotic process was monitored with a Doppler during a 30-min observation period for cyclic flow reductions or permanent cessation of flow; after the first cyclic flow reduction occurred, clopidogrel (5 mg kg-1) or aspirin (2.5, 5, 100 mg kg-1) were injected intravenously; if cyclic flow reductions were abolished, epinephrine (0.4 micrograms kg-1 min-1) was injected to try to restore cyclic flow reductions and/or permanent cessation of flow; then injury and stenosis were applied on the right femoral artery. Before and after injection of clopidogrel or aspirin, ear immersion bleeding times and ex-vivo platelet aggregation were performed. Clopidogrel (n = 7) abolished cyclic flow reductions were efficiently prevented, even for two injuries. Basal bleeding time (5 min 28) was lengthened (> 15 min, 30 min after clopidogrel and remained prolonged even after 24 h). ADP-induced platelet aggregation was inhibited (more than 78%). Comparatively, aspirin had a moderate and no dose-dependent effect. Aspirin 2.5 mg kg-1 (n = 6) abolished cyclic flow reductions in 2 animals, CFR reoccurred spontaneously in one animal and epinephrine restored it in a second animal.(ABSTRACT TRUNCATED AT 250 WORDS)


Plasminogen levels in healthy volunteers--influence of age, sex, smoking and oral contraceptives. There is considerable doubt as to the importance of reduced plasminogen (PLG) activity as a risk factor for venous thrombosis. In the present study we have identified a wide range of PLG activities (25-200%) in a cohort of 9,611 blood donors. Males and females not taking hormonal contraceptives show a similar distribution of PLG, however, variation related to age appears to follow a different pattern in males and females. These differences are of doubtful clinical importance as are differences related to smoking. In contrast, females taking hormonal contraceptives or hormone replacement therapy (HRT) have up to 25% higher mean PLG levels in younger females but a less marked elevation (10%) is seen in 40-50 year olds. A PLG activity < 65% was recorded in 61 donors, none of whom appeared to have a history of thrombosis. These findings do not support the notion that reduced PLG is an important thrombophilic risk factor, however, further investigation of the donors with low PLG is required.


A novel rat model of thrombogenicity: its use in evaluation of prothrombin complex concentrates and high purity factor IX concentrates. A non-stasis rodent model of thrombogenicity has been used for dose-ranging studies with a conventional prothrombin complex concentrate (PCC) and to evaluate high purity factor IX concentrates from different manufacturers. Fibrin monomer (soluble fibrin) and fibrinopeptide A (FPA) were monitored before and after infusion of test solution. FPA was found to be the more sensitive and reproducible indicator of thrombogenicity and exhibited a dose-related elevation after infusion of the PCC at doses of between 100-300 IU/kg. In contrast the amounts of FPA generated after 300 IU/kg of the high purity factor IX products were similar to control infusions of albumin.


Fibrinolytic potential and antiphospholipid antibodies in systemic lupus erythematosus and other connective tissue disorders. We studied the fibrinolytic response before and after venous occlusion (VO) in 30 patients with systemic lupus erythematosus (SLE), 25 with rheumatoid arthritis (RA) and 25 with different connective tissue disorders. Results were compared in patients with and without antiphospholipid antibodies (APA) and a history of either thrombosis or abortions. Before occlusion plasma levels of tissue-type plasminogen activator (t-PA) antigen and its inhibitor (PAI-1) were significantly higher in the patient group (p < 0.001). After occlusion, a low fibrinolytic activity on fibrin plates (p < 0.005) was observed in the same group. t-PA capacity and t-PA release were similar in relation to controls. The plasma PAI-1 activity was significantly elevated in each group of patients (p < 0.005) as compared to the control group. No significant differences with respect to t-PA and PAI-1 were observed in patients as to the presence or absence of thrombosis. There was also no correlation between the fibrinolytic changes and the presence of APA. It is concluded that an impairment of the fibrinolytic system, mainly related to increased PAI-1 levels, is present in most patients with connective tissue disorders, although these changes did not correlate with the presence of APA or the incidence of thrombosis.


Congenital deficiency of all vitamin K-dependent blood coagulation factors due to a defective vitamin K-dependent carboxylase in Devon Rex cats. Two Devon Rex cats from the same litter, which had no evidence of liver disease, malabsorption of vitamin K or chronic ingestion of coumarin derivatives, were found to have plasma deficiencies of factors II, VII, IX and X. Oral treatment with vitamin K1 resulted in the normalization of these coagulation factors. After taking liver biopsies it was demonstrated that the coagulation abnormality was accompanied by a defective gamma-glutamyl-carboxylase, which had a decreased affinity for both vitamin K hydroquinone and propeptide. This observation prompted us to study in a well-defined in vitro system the possible allosteric interaction between the propeptide binding site and the vitamin K hydroquinone binding site on carboxylase. It was shown that by the binding of a propeptide-containing substrate to gamma-glutamylcarboxylase the apparent KM for vitamin K hydroquinone is decreased about 20-fold. On the basis of these in vitro data the observed defect in the Devon Rex cats can be fully explained.


Structure, kinetics, and function of human and rhesus plasma prekallikreins are similar. To determine if rhesus monkeys (Macaca mulatta) could serve as a model for studying the role of the contact system in the pathophysiology of human infections, we compared structural, kinetic, and functional characteristics of plasma prekallikrein and its activation products in rhesus and humans. Three prekallikrein variants (85-, 89- and 93-kDa) were revealed in rhesus plasma as compared with the two variants (85- and 88-kDa) in human plasma by immunoblotting with the monoclonal antibody MAb 13G11. The prekallikrein concentration in rhesus plasma was 1.5-fold that in human plasma as determined by computerized immunoblot analyses (CIBA) and amidolytic activity. The electrophoretic mobility of prekallikrein from plasma of both species increased after deglycosylation. Inhibition of prekallikrein activation by MAb 13G11 was 55% (rhesus plasma) and 76% (human plasma), with similar inhibition curves. Immunoblots of activated rhesus plasma showed prekallikrein, complexes of kallikrein with C1 inhibitor, alpha 2-macroglobulin and approximately 60-kDa inhibitor(s) (viz. antithrombin III), and 45-kDa fragments, like those in activated human plasma. Concentrations and molecular masses of factor XII and high molecular weight kininogen were similar in rhesus and human plasma. The activated partial thromboplastin time (APTT) and prothrombin time were 20.1 +/- 1.6 and 9.7 +/- 0.3 s for rhesus and 32.0 +/- 5.6 and 12 +/- 0.5 s for human plasma. Human and rhesus APTTs were similar when prekallikrein concentrations in human and rhesus plasma became alike by adding human purified prekallikrein.(ABSTRACT TRUNCATED AT 250 WORDS)


Heterozygous abnormal fibrinogen Osaka III with the replacement of gamma arginine-275 by histidine has an apparently higher molecular weight gamma-chain variant. Congenitally abnormal fibrinogen Osaka III with the replacement of gamma Arg-275 by His was found in a 38-year-old female with no bleeding or thrombotic tendency. Release of fibrinopeptide(s) by thrombin or reptilase was normal, but her thrombin or reptilase time in the absence of calcium was markedly prolonged and the polymerization of preformed fibrin monomer which was prepared by the treatment of fibrinogen with thrombin or reptilase was also markedly defective. Propositus' fibrinogen had normal crosslinking abilities of alpha- and gamma-chains. Analysis of fibrinogen chains on sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) in the system of Laemmli only revealed the presence of abnormal gamma-chain with an apparently higher molecular weight, the presence of which was more clearly detected with SDS-PAGE of fibrin monomer obtained by thrombin treatment. Purified fragment D1 of fibrinogen Osaka III also seemed to contain an apparently higher molecular weight fragment D1 gamma remnant on Laemmli gels, which was digested faster than the normal control by plasmin in the presence of [ethylenebis(oxyethylenenitrilo)]tetraacetic acid (EGTA).


The influence of glycosylation on the catalytic and fibrinolytic properties of pro-urokinase. We previously found that human pro-UK expressed in Escherichia coli is more active in fibrinolysis than recombinant human pro-UK obtained from mammalian cell culture media. To determine whether this difference is related to the lack of glycosylation of the E. coli product, we compared the activity of E. coli-derived pro-UK [(-)pro-UK] with that of a glycosylated pro-UK [(+)pro-UK] and of a mutant of pro-UK missing the glycosylation site at Asn-302 [(-)(302)pro-UK]. The latter two pro-UKs were obtained by expression of the human gene in a mammalian cell. The nonglycosylated pro-UKs were activated by plasmin more efficiently (approximately 2-fold) and were more active in clot lysis (1.5-fold) than the (+)pro-UK. Similarly, the nonglycosylated two-chain derivatives (UKs) were more active against plasminogen and were more rapidly inactivated by plasma inhibitors than the (+)UK. These findings indicate that glycosylation at Asn-302 influences the activity of pro-UK/UK and could be the major factor responsible for the enhanced activity of E. coli-derived pro-UK.


Antithrombotic properties of dermatan sulphate (MF 701) in haemodialysis for chronic renal failure. The therapeutic potential of the glycosaminoglycan (GAG), dermatan sulphate (DS), as an antithrombotic agent in humans has yet to be established. We have performed dose ranging studies of DS to determine its effectiveness as an antithrombotic agent in patients (n = 6-8) undergoing haemodialysis for chronic renal failure. In an initial study, Study 1, i.v. bolus doses of 2-4 mg/kg and 5-6 mg/kg DS were given to patients dialysing with polyacrylonitrile hollow fibre (PAN HF) membranes. In a second crossover study, Study 2, performed using cuprophane hollow fibre (CHF) membranes, i.v. bolus doses of 3 mg/kg and 6 mg/kg DS were compared to a standard unfractionated heparin (UFH) regime that has been shown previously to inhibit fibrin formation. Further infusion studies, Study 3 and Study 4 evaluated the antithrombotic efficacy of an i.v. DS bolus of 3 mg/kg plus an i.v. infusion of DS 0.6 mg kg-1 h-1 and a DS bolus of 5 mg/kg plus an infusion of 1 mg kg-1 h-1 over 5 h, respectively. These studies were compared to standard UFH regimes in a randomised crossover design. Plasma levels of fibrinopeptide A (FPA) and thrombin-antithrombin (TAT) were used as markers of fibrin formation and thrombin generation during dialysis using both membranes. The changes in DS concentration following administration of the different doses were similar in Studies 1 and 2. However, the effectiveness of DS as an anticoagulant appeared to depend markedly on the different dialyser types used in the two studies.(ABSTRACT TRUNCATED AT 250 WORDS)


Adrenergic stimulation of regional plasminogen activator release in rabbits. The purpose of this study was to determine whether different regions of the rabbit vascular system show variations in the rate of plasminogen activator (PA) secretion. To start, we evaluated the time course, dose response and adrenergic specificity of PA release. Infusion of 1 microgram/kg of epinephrine stimulated a 116 +/- 60% (SD) increase in PA activity that peaked 30 to 60 s after epinephrine administration. Infusion of 1 microgram/kg of norepinephrine, isoproterenol and phenylephrine had no effect on PA activity. Pretreatment with phentolamine, an alpha adrenergic antagonist, blocked the release of PA by epinephrine while pretreatment with the beta blocker propranolol had no effect. This suggests that PA release in the rabbit was mediated by some form of alpha receptor. Significant arterio-venous differences in basal PA activity were found across the pulmonary and splanchnic vascular beds but not the lower extremity/pelvic bed. After stimulation with epinephrine, PA activity increased 46% across the splanchnic bed while no change was seen across the lower extremity/pelvic bed. We conclude that several vascular beds contribute to circulating PA activity in the rabbit, and that these beds secrete PA at different rates under both basal and stimulated conditions.


Decreased platelet membrane fluidity due to glycation or acetylation of membrane proteins. Platelets from diabetic subjects and animals are hypersensitive to agonists in vitro. Membrane fluidity modulates cell function and previously we observed reduced membrane fluidity in platelets from diabetic patients associated with hypersensitivity to thrombin. We previously reported that decreased fluidity of isolated platelet membranes from diabetic patients is associated with increased glycation of platelet membrane proteins, but not with any change in the cholesterol to phospholipid molar ratio. We have now examined in vitro whether incubation of platelet membranes in a high glucose medium causes sufficient glycation to reduce membrane fluidity. Incubation of platelet membranes from control subjects in a high glucose (16.1 mM) medium for 10 days at 37 degrees C led to an increase in the extent of glycation of membrane proteins and a decrease in membrane fluidity (indicated by an increase in steady state fluorescence polarization); most of the changes occurred within the first 3 days of incubation. Incubation of platelet membranes with 5.4 mM glucose had less effect. In contrast, incubation of platelet membranes with the same concentrations of 1-0-methylglucose did not cause a change in either the extent of glycation of proteins or membrane fluidity. We also determined if acetylation by aspirin or acetyl chloride of the sites available for glycation on platelet membrane proteins leads to a similar reduction in membrane fluidity. Pretreatment of platelet membranes with aspirin or acetyl chloride diminished the extent of glycation that occurred when platelet membranes were subsequently incubated with glucose, but membrane fluidity was reduced even in the absence of glucose; subsequent incubation with glucose caused no further reduction in membrane fluidity.(ABSTRACT TRUNCATED AT 250 WORDS)


Cigarette smoking increases thromboxane A2 formation without affecting platelet survival in young healthy females. Smoking is a risk factor for the development of atherosclerotic cardiovascular disease, in men as well as in women. An increased urinary excretion of the thromboxane metabolite 2,3-dinorthromboxane B2 (Tx-M) has been observed in smokers of both genders, suggesting that cigarette smoking may facilitate cardiovascular disease via an action on the platelets. The present study addressed the hypothesis that the increased Tx-M excretion in female smokers reflects a true facilitation of platelet reactivity in vivo, rather than an increased destruction of the platelets. In healthy female volunteers (aged 20-46 years, 18 smokers and 17 non-smokers) platelet life-span and indices of platelet activity were determined, together with plasma levels of plasminogen activator inhibitor-1 (PAI-1), fibrinogen, peripheral blood cell counts and hematocrit. The urinary excretion of Tx-M was higher in smokers than in non-smokers (361 vs. 204 pg/mg creatinine, respectively, p < 0.05), while plasma and urinary beta-thromboglobulin, plasma platelet factor 4, platelet mean life-span and platelet production rate did not differ between the groups. PAI-1 activity, white blood cell count and hematocrit were higher in smokers than in non-smokers (p < 0.05). These data indicate that smoking facilitates platelet formation of thromboxane A2 without affecting platelet survival; i.e. it increases the activity of platelets without affecting their viability to a measurable extent. Such an increase in platelet activity, operating in parallel to a reduced fibrinolytic activity and a higher hematocrit and white blood cell count, may play an etiological role in smoking-induced cardiovascular disease in women.


Human platelets exposed to mechanical stresses express a potent lipoxygenase product. Human platelets exposed to hypotonicity undergo regulatory volume decrease (RVD), controlled by a potent, yet labile, lipoxygenase product (LP). LP is synthesized and excreted during RVD affecting selectively K+ permeability. LP is assayed by its capacity to reconstitute RVD when lipoxygenase is blocked. Centrifugation for preparing washed platelets (1,550 x g, 10 min) is sufficient to express LP activity, with declining potency in repeated centrifugations, indicating that it is not readily replenishable. When platelet suspension flows in a vinyl tubing (1 mm i.d.), at physiological velocity, controlled at 90-254 cm/s, LP formation increases as a function of velocity but declines as result of increasing the tubing length. Stirring the platelets in an aggregometer cuvette for 30 s, yields no LP unless the stirring is intermittent. No associated platelet lysis or aggregation are observed following the mechanical stress applications. These results demonstrate that although mechanical stresses result in LP production, the mode of its application plays a major role. These results may indicate that LP is synthesized under pathological conditions and could be of relevance to platelets behavior related to arterial stenosis.


Stored platelets release nucleotides as inhibitors of platelet function. It is well known that the function of platelets decreases progressively during storage of platelet concentrates at room temperature. To investigate this phenomenon in more detail, we have resuspended platelets that had been stored for 24 h or 72 h in fresh plasma, and we have measured the aggregation response and the ATP secretion. Conversely, the effect of plasma in which platelet concentrates (PC) had been stored for 24 h or 72 h, was tested on fresh platelets. Both the aggregation response to collagen and ADP and the collagen-induced ATP secretion of stored platelets partially recovered after incubation with fresh plasma (p < 0.05). The same parameters measured with fresh platelets incubated in stored PC-plasma were found to be significantly reduced in comparison with the response of fresh platelets in fresh plasma (p < 0.05). Finally, platelets were stored in a plasma-free medium, suitable for platelet storage and the supernatant was tested. This supernatant inhibited the function of fresh platelets in a storage time-dependent fashion. Boiling of these supernatants did not change the inhibiting capacities, whereas filtration over active charcoal did. Analysis of this supernatant revealed AMP and diadenosine tetraphosphate, which both inhibit platelet function. These data show that stored platelets release nucleotides that inhibit platelet function in a reversible manner. This phenomenon may contribute to the decrease of platelet function during storage and the recovery of platelet function after transfusion.


Computer-assisted three-dimensional volumetry of the human pulmonary acini. Computer-aided three-dimensional (3-D) volumetry of human pulmonary acini was undertaken using the left upper lobe of a 51-year-old female operated for small lung cancer. A normal part of this lobe, fixed by intrabronchial infusion with a mixture of polyethylene glycol and formalin, was subjected to serial sectioning, using a special slicer, into 48 serial slices of 0.5 mm in thickness. A soft x-ray radiograph was prepared from each slice at x 12, and the contours of airways and acinar boundaries contained in it were input by digitization into a microcomputer for 3-D reconstruction and volumetry. The estimated volumes of 130 acini were unexpectedly uniform, showing a normal type distribution with a mean of 172.7 +/- 37.9 mm3. No significant correlation proved to exist between the volume of acini and the number of branching generation of the terminal bronchioles (TBs) they received. Furthermore, there was no significant difference in volume among the acini facing the costal surface, those facing the mediastinal surface and those not facing any pleural surface. However, the generation number of TBs was shown to differ significantly with the location of acini. These results suggest that the tree of conductive airways is designed so as to meet the requirement of constant acinar volume.


Prevalence of HTLV-I antibody in pulmonary cryptococcosis. A retrospective study was done to determine the prevalence of anti-HTLV-I antibodies in patients with pulmonary cryptococcosis. None of the 19 patients with pulmonary cryptococcosis had underlying immunodeficiency. Anti-HTLV-I antibody was present in 6 (32%) of 19 patients with pulmonary cryptococcosis, a significantly higher prevalence than found in patients with bronchial asthma (4 (7%) of 58) (p less than 0.01, chi-square test). No statistical difference was noted when anti-HTLV-I antibody seropositivity was compared to that of patients with pulmonary tuberculosis (16% (17/105)), lung cancer (17% (22/129)) and pneumonia (9% (6/64)). A reduced cellular immunity as shown by lymphopenia, the CD4/CD8 ratio, and purified protein derivative skin test was found in only 1 (5%) of 19, 2 (12%) of 17, and 6 (33%) of 18 patients, respectively. These results do not explain the susceptibility to pulmonary cryptococcosis in HTLV-I carriers. This is the first report of high prevalence of pulmonary cryptococcosis in HTLV-I carriers and it raises the question whether HTLV-I carriers are more susceptible to opportunistic infections and other malignancies probably due to subtle immunological abnormalities.


The effects of intrarenal infusion of recombinant human erythropoietin on mean arterial pressure and renal hemodynamics in anesthetized rabbits. The effects of recombinant human erythropoietin (rHuEPO) on mean arterial pressure (MAP) and renal hemodynamics were studied in anesthetized rabbits without renal failure. Intrarenal infusion of rHuEPO at a rate of 100 U/min for 30 min resulted in no change in MAP, renal blood flow, or renal vascular resistance. rHuEPO also produced no significant change in glomerular filtration rate filtration fraction, or arterial hematocrit. These results demonstrate that rHuEPO has no direct effects on MAP or renal hemodynamics in anesthetized rabbits without renal failure.


Histopathological evaluation on the effect of induced hypertension chemotherapy presurgically performed in patients with advanced carcinoma of the stomach. Stomachs resected from 13 patients with an advanced gastric carcinoma were examined histopathologically to evaluate the effect of induced hypertension chemotherapy (IHC) using angiotensin II. Eight of the 13 patients, randomly chosen, were treated presurgically by IHC with a regimen of 5-fluorouracil, adriamycin and mitomycin C; the same regimen was used in the remaining five patients but without inducing hypertension. Clinical evaluation of the effect gave rise to the confirmation, presurgically, of complete response in three and partial response (PR) in two patients in the IHC group, whereas in the non-IHC group, the highest rating was PR, which was attained in only one patient. Also in the histopathological assessment based on a five-step grading, the IHC group earned in average a higher score than the non-IHC group, with a difference proved significant by Wilcoxon's test. A histological rating of Grade 3, the highest effectiveness, was given to three patients in the IHC group, in one of whom the resected stomach disclosed no viable carcinoma cells but only fibrotic areas replacing carcinoma. There was also a correlation between the clinical and histological ratings as proved to be significant by Spearman's test. We conclude that in gastric carcinoma, the effect of chemotherapy is enhanced by angiotensin II-IHC.