Frozen shoulder: a sympathetic dystrophy?

Diagnostic and clinical features of the frozen shoulder syndrome and the Sudeck syndrome are similar in many aspects. Radioisotope bone scan shows an increased uptake in affected areas in both diseases, while native radiographs show a progressive demineralisation. Measurement of bone mineral density (BMD) by quantitative digital radiography objectified these local decalcification processes in an early stage of the frozen shoulder syndrome; 10 of 12 patients with primary frozen shoulder had BMD decreases greater 21% in the humeral head of the affected shoulder compared to the non-affected side. In the immobilised control group with degenerative changes of the rotator cuff, calcifying tendinitis and shoulder instability (n = 12) and in the group of healthy probands (n = 20), the difference between the affected and non-affected side (left and right humerus of the healthy probands) was only more than 21% in one case each. There are several references in the literature that assume frozen shoulder to be an algoneurodystrophic process; our observations support this hypothesis, possibly leading to earlier diagnoses and extended therapeutic management.

Oral budesonide and ursodeoxycholic acid for treatment of primary biliary cirrhosis: results of a prospective double-blind trial.

BACKGROUND & AIMS: Ursodeoxycholic acid (UDCA) is used for treatment of primary biliary cirrhosis. Previous studies showed that, compared with UDCA monotherapy, bile salts plus prednisolone had no further effect on laboratory data but improved liver histology. Thirty percent of these patients had prednisolone-related side effects. Budesonide is a glucocorticoid with a high receptor affinity and a high first-pass metabolism. In this study we investigated whether budesonide and UDCA are superior to UDCA monotherapy. METHODS: A 2-year prospective, controlled double-blind trial was performed. Twenty patients (mainly with early-stage disease) were treated with UDCA at a dose of 10-15 mg/kg daily in addition to 3 mg budesonide 3 times daily (group A), and 19 patients (1 dropped out for personal reasons) were treated with UDCA plus placebo (group B). Liver biopsy specimens were taken before, after 12 months, and at the end of study. Glucose tolerance tests, serum cortisol levels, and adrenocorticotropin-stimulated cortisol secretion were assessed at regular intervals. Bone mass density was measured by dual-energy photon absorptiometry. RESULTS: Compared with pretreatment values, liver enzyme and immunoglobulin M and G levels decreased significantly in both groups. Improvement in group A was significantly more pronounced (P < 0.05) than in group B. Titers of antimitochondrial antibodies did not change. In group A, the point score of liver histology improved by 30.3%; in group B, it deteriorated by 3.5% (P < 0.001). Changes in bone mineral density after 2 years were -1.747% in group A and -0.983% in group B (P = 0.43). Budesonide had little influence on the hypothalamic-pituitary-adrenal axis. One patient in group A had budesonide-related side effects; in 3 patients in group B, complications of liver disease developed. CONCLUSIONS: Combination therapy with UDCA and budesonide is superior to UDCA and placebo.

Frozen shoulder--an algoneurodystrophic process?

The frozen shoulder syndrome and the Sudeck syndrome are clinically in many aspects similar. Radioisotope bone scan shows an increased uptake in the affected areas in both diseases, while standard radiographs show a progressive demineralization. With measurement of bone-mineral density by quantitative digital radiography these local decalcification processes were diagnosed in an early stage of the frozen shoulder syndrome: of 12 patients with primary frozen shoulder 10 had a bone-mineral density decrease of more than 21% in the humeral head of the affected shoulder compared to the unaffected side. In the control groups (n = 32) the difference between affected and unaffected side (left and right humerus of the healthy probands) was in only one case each above 21%. There are several indications in the literature assuming the frozen shoulder to be an algoneurodystrophic process. Our observation supports this hypothesis, and may possibly lead to earlier diagnosis and improved therapeutic management.

[Quantitative determination of echogenicity of diffuse inflammatory thyroid gland diseases]. / Quantitative Bestimmung der Echogenität diffus entzündlicher Schilddrüsenerkrankungen.

Grey level was measured in 93 ultrasonic scans of the thyroid gland in order to quantify hypoechogenicity in diffuse inflammatory thyroid disease. Using a modern ultrasound device (256 grey-scale steps and 7.5-MHz parallel scan), grey levels were measured in normal thyroid glands and euthyreotic goiters as well as in thyroiditis or Graves' disease using a programmed setting of the device. Highly significant differences were found between normal thyroid glands and thyroiditis or Graves' disease. Sensitivity of the method was 65% in discriminating Graves' disease and 91% in discriminating thyroiditis; specificity was 95%. The clinical value of the method for follow-up studies in inflammatory diseases of the thyroid gland still has to be established.

Subcutaneous gonadotropin therapy in male patients with hypogonadotropic hypogonadism.

OBJECTIVE: The response to subcutaneous (SC) gonadotropin replacement therapy, using human chorionic gonadotropin (hCG) and human menopausal gonadotropin (hMG) or hCG alone, was evaluated in male hypothalamic hypogonadism. DESIGN: Sixteen patients with hypothalamic hypogonadism were treated with gonadotropins for induction of puberty and normalization of spermatogenesis. The results were analyzed retrospectively. SETTING: The study was carried out in a clinical endocrinology department providing tertiary care and in private practices of endocrinology. PATIENTS: Eight patients with idiopathic hypogonadotropic hypogonadism and eight patients with Kallmann's syndrome in prepubertal or early pubertal stages. INTERVENTIONS: Human chorionic gonadotropin and hMG were administered SC in individual dosages. MAIN OUTCOME MEASURES: Increase of serum testosterone (T), testicular volume, semen volume, and sperm count were evaluated. RESULTS: Normalization of serum T and complete sexual maturation was achieved in all patients. Spermatogenesis was induced in all but two patients. Seven patients showed normal findings in semen volume and sperm count, and two patients had semen quality close to normal. In five patients sperm count remained less than 10 x 10(6)/mL. CONCLUSIONS: The results obtained by SC gonadotropin replacement prove this mode of administration to be effective in stimulating steroidogenesis and spermatogenesis in hypogonadotropic males.

Pharmacodynamics and pharmacokinetics after subcutaneous and intramuscular injection of human chorionic gonadotropin.

OBJECTIVE: The pharmacokinetics and efficiency of human chorionic gonadotropin (hCG) after subcutaneous (SC) injection was to clarify in comparison with the intramuscular (IM) mode of administration. DESIGN: In a prospective study, the pharmacokinetics of hCG and the response of serum testosterone (T), luteinizing hormone (LH), and follicle-stimulating hormone (FSH) after an IM and SC injection of 5,000 IU hCG were evaluated up to 144 hours in two randomized groups. SETTING: The study was carried out in a clinical dermatology department providing tertiary care. PARTICIPANTS: Twenty-four healthy male volunteers with a mean age of 22.7 +/- 4.3 years were divided into two groups. INTERVENTIONS: Human chorionic gonadotropin (5,000 IU) was injected IM or SC. MAIN OUTCOME MEASURE: Serum concentration of /b-hCG, T, LH, and FSH were evaluated after IM and SC administration of hCG. Differences between the two groups were determined by t-test. RESULTS: Compared with IM administration of hCG, peak serum drug concentration was significantly delayed (P = 0.01) and serum half-life was prolonged (P = 0.01) after SC injection; however, T, LH, and FSH responses were identical. CONCLUSIONS: Subcutaneous application of 5,000 IU hCG is as effective as IM administration in terms of steroidogenesis.

Early immunoscintigraphic localisation of a mediastinal tumour with indium 111-DTPA CEA-specific F(ab')2 monoclonal antibody fragments (BW 431/31) using second tracer isocontour technique.

A female patient with steadily increasing carcinoembryonic antigen (CEA) serum levels of unknown origin was referred for immunoscintigraphy with indium 111-labelled CEA-specific monoclonal antibody. The procedure revealed a tumour, undetectable by conventional diagnostic methods. Anatomical landmarking using the second tracer isocontour technique allowed the distinction between an intra- or extrapulmonary lesion. Two months later, tumour infiltration along the aortic arch was confirmed by a targeted angio-CT scan. Upon surgery, the diagnosis was definitely established histologically (undifferentiated, solid large cell carcinoma, most probably arising from the bronchus), and staining by CEA-specific immunohistochemistry confirmed the presence of the CEA antigen.

[The surgical concept of malignant melanoma with special reference to lymphatic drainage scintigraphy]. / Zum operativen Konzept beim malignen Melanom unter Berücksichtigung der Lymphabstromszintigraphie.

Scintigraphy of the lymphatic vessels was performed in 29 patients with malignant melanoma of the skin (stage I) prior to operation. In 20 cases this procedure was a means of determining the course of the lymphatic vessels leading from the tumor to the respective lymphatic nodules. The lymphatic vessels were indicated by marks on the skin surface and could thus be taken into consideration in the surgical procedure. The parts of the lymphatic vessels adjacent to the tumor were removed without substantially prolonging the operation. This procedure is intended to help minimize the risk of metastases evolving.

Radioimmunoscintigraphy using monoclonal antibodies to CEA, CA 19-9 and CA 125.

131I labelled F (ab')2 fragments of monoclonal antibodies against CA 19-9 and CEA ("radioimmunococktail" IMACIS 1) were used in a prospective study (n = 60 patients) and in a retrospective study (n = 32 patients) for the detection of colorectal carcinomas (n = 67) and other gastrointestinal CEA/CA 19-9-producing tumors (n = 32). Sensitivity was 82% and specificity 90%. Immunoscintigraphy proved useful and complementary to CT scan and sonography, especially in the diagnosis of pelvic recurrences and intra-abdominal metastases. In addition, monoclonal antibody OC 125 (IMACIS 2) was used for the detection of ovarian carcinomas (n = 10) and other CA 125 producing tumors. Immunoscintigraphy was positive in all patients (n = 18) suggesting that this radioimmunological approach could be of use in the staging, therapeutic control and earlier diagnosis of recurrent epithelial ovarian carcinoma.

MIBG-treatment in neuroblastoma; experiences of the Tübingen/Frankfurt group.

27 children with neuroblastoma were treated with 131I-Metaiodobenzylguanidine (MBIG). They were either refractory to conventional therapy or experienced relapse after initially successful treatment. 7 children revealed stage IV and 20 stage III at the beginning of MIBG-treatment. MIBG was administered by infusion lasting from 30 min to 30 hrs. In most children the dose was split into two portions each infused over a period of 4 hrs with a 24 hrs interval between. Courses were repeated up to 6 times and maximum activity given to one patient cumulatively was 38,221 MBq. 24 patients were evaluable for analysis of results. In 4 children (16.7%) a CR was observed, in 10 (41.7%) a PR, in 5 (20.8%) a disease stabilization and 5 were nonresponders. The 4 CR-patients were initially stage IV. 3 of them were treated in addition by bone marrow transplantation (bmt), one by further chemotherapy. 3 died of a relapse, 1 of complications from bmt. 5 of the 10 PR-patients died of tumor progression, 3 achieved a CR by additional chemotherapy, 1 a PR by bmt and 1 stays in PR without further measures. 2 of the 5 children with a disease stabilization were the first treated patients to whom a fairly low dose was given. In 3 of the 5 nonresponders no uptake of MIBG was observed; they died from tumor progression. 1 of the 2 nonresponders with uptake died of graft-versus-host disease after bmt, 1 other also of tumor progression. Duration of remission was between 1 and 12 months and depended upon uptake and dose of MIBG, interval between administrations and individual tumor behaviour. Side effects were seen as marked bone marrow depression; this was reversible in any case and we did not loose a patient due to MIBG-induced leuko- or thrombopenia. In cases of severely ill children we observed a very fast and dramatical amelioration in clinical conditions. With this method even in neuroblastoma relapse and in nonresponders complete remissions are achievable. Important is the intensification of the therapeutical effect by additional chemotherapy or in combination with bmt. For a definitive evaluation further investigations are necessary to optimize therapeutic strategies.

[Immunoscintigraphy using 111In-DTPA-labeled monoclonal antibodies: comparison with ECT and planar scintigraphy]. / Immunszintigraphie mit 111In-DTPA-markierten monoklonalen Antikörpern: Vergleich zwischen ECT und planarer Szintigraphie.

The present study was done in order to examine if the use of 111In-DTPA-labeled MAb fragments in place of 131I-labeled MAb fragments increases the sensitivity of tomographic immunoscintigraphy to reach the level of that of planar imaging techniques. In 11 patients with various primary tumors, local recurrences or metastases [colorectal carcinoma (n = 7), ovarian carcinoma (n = 2), papillary thyroid carcinoma (n = 1), undifferentiated carcinoma of the lung (n = 1)], immunoscintigraphy (IS) was carried out using 111In-DTPA-labeled F(ab')2 fragments of various MAbs (anti-CEA, OC 125, anti-hTG) and planar and tomographic imaging were compared intra-individually. By conventional diagnostic procedures, the presence of a tumor mass was confirmed (transmission computer tomography, ultrasound) or verified (131I whole-body scintigraphy, histology) in all cases. Immunoscintigraphy was positive in 9 out of 11 cases by ECT and in 10 out of 11 cases by planar imaging. When using 111In-labeled MAb fragments, intra-individual comparison of ECT and planar imaging resulted in a similar sensitivity. The increased sensitivity of ECT using this tracer in contrast to 131I-labeled MAb fragments may be attributed to the fact that the physical properties of 111In are much more suitable for the gamma cameras most commonly used (single detector, 3/8'' crystal); using 111In-labeled MAb fragments, count rates sufficient for ECT can be obtained within a reasonable acquisition time. This allows to combine IS with the advantages of ECT regarding tumour localization and prevention of artefacts due to superposition of background.

Stimulation of spermatogenesis and biological paternity by intranasal (low dose) gonadotropin-releasing hormone (GnRH) in a male with Kallmann's syndrome: intraindividual comparison of GnRH and gonadotropins for stimulation of spermatogenesis.

Intranasal (in) GnRH spray caused induction and maintenance of spermatogenesis and biological paternity in a 28-yr-old man with Kallmann's syndrome. Prior treatment had included GnRH analog administration, which failed to induce puberty, and testosterone (T) enanthate weekly. Prior hCG/human menopausal gonadotropin therapy had resulted in high normal serum T levels and near-normal semen quality, but during subsequent hCG therapy, spermatogenesis markedly decreased. The patient had then received 250 mg T enanthate/month for 2 yr and 7 months; it was discontinued 7 weeks before the in GnRH study began. At its start (July 1984) the subject's testis size was 7 mL, and he had azoospermia, low serum LH and FSH levels, and a serum T of 74 ng/dL (2.6 nmol/L). GnRH was administered in a dose of 200 micrograms (20-120 ng/kg were absorbed into the circulation) every 2 h, seven to nine times a day, between 0700 and 2400 h for 242 days. After 12 days of treatment, serum T had increased to 519 ng/dL (18.0 nmol/L). After 70 days, the patient's sperm count was 11.5 million/mL (4.5 mL ejaculate volume; 70% motility; 36% normal morphology); on day 185, sperm count was 31 million/mL (4 mL ejaculate volume; 54% motility; 36% normal morphology). His spouse conceived on day 162 and delivered a fullterm daughter 265 days later. The probability of paternity was 99.9994%. Our results suggest that induction and maintenance of spermatogenesis as well as fertility in hypothalamic hypogonadism can be achieved with in GnRH therapy if pituitary and testicular function are intact. Spermatogenesis induced by in GnRH has the same quality as spermatogenesis induced by hCG/human menopausal gonadotropin therapy. Patient compliance is probably the most important factor for the success of in GnRH therapy.

131-Metaiodobenzylguanedine therapy of neuroblastoma in childhood. One year of therapeutic experience.

Eleven children with neuroblastoma refractory to conventional therapy or relapse of neuroblastoma were treated with 131-metaiodobenzylguanedine (MIBG). The therapeutic results and the side effects were evaluated. In one patient with disseminated bone marrow involvement complete remission was obtained. Partial remission was observed in six patients and stable disease in another. Three patients did not respond to MIBG, in two of them the tumours did not accumulate a sufficient MIBG dose. Clinical and laboratory examinations revealed an excellent tolerance of MIBG in all patients. First attempts to continue cytostasis after MIBG therapy were made. MIBG has a good therapeutic efficacy is sufficiently incorporated into the tumour cell.

Radionuclide ventriculography: acute and chronic response to verapamil in patients with hypertrophic cardiomyopathy.

Eleven patients with hypertrophic cardiomyopathy were investigated by repeated radionuclide ventriculography. Nine of them were studied for the first time while under long-term treatment for 14 to 84 months. In all eleven patients radionuclide ventriculography was performed after a withdraw of verapamil for at least 14 days or before the onset of therapy respectively (control period). A third investigation was carried out 60 to 90 min after acute administration of 90 mg oral verapamil. A last radionuclide ventriculography was performed following 2 weeks of therapy with 480 mg oral verapamil. After acute administration heart rate significantly increased from 69 +/- 10 to 80 +/- 15/min. EDV was in the normal range. Left ventricular global ejection parameters showed no significant changes except for minimal decrease in ejection time from 309 +/- 29 to 278 +/- 50 ms after acute verapamil administration. The sectorial ejection fraction improved in apical sectors in relation to the basal one, while the global EF remained constant. The ventricular global peak filling rate increased significantly from 283 +/- 61 to 325 +/- 64%/EDV/s after acute administration of verapamil and the sectorial peak filling rate increased in apical sectors compared to basal sectors following acute administration as well as long-term therapy. After withdrawal of verapamil, six out of 11 patients showed a homogeneous left ventricular delay of contraction by means of the Fourier phases which were normalized under short- and long-term verapamil treatment. In conclusion, verapamil caused a marked improvement of the left ventricular contraction delay without significant changes in global systolic function.

[Induction of puberty by pulsatile luteinizing hormone releasing hormone (LH-RH)--therapy in a boy with Kallmann syndrome]. / Einleitung der Pubertät durch pulsatile Luteinisierungshormon-Releasing-Hormon (LH-RH)--Therapie bei einem Jungen mit Kallmann-Syndrom.

To induce the lacking development of puberty, a male patient with hypothalamic hypogonadism and anosmia (Kallmann's syndrome) was treated with pulsatile application of gonadotropin-releasing hormone (GnRH) to imitate the endogenous secretion of GnRH. The low-dose pulsatile GnRH treatment which was reported to be successful by various authors proved to be ineffective when administered to our patient subcutaneously as well as intravenously. Serum testosterone levels comparable to the lower normal values in adults and continuous progress of pubertal development were only achieved after increasing the dosage from 2 to 8 micrograms per pulse by subcutaneous application. The course of therapy is reported in detail.

[Clinical evaluation of the tumor marker CA 19-9 in comparison with carcinoembryonic antigen (CEA) in surgical pre- and postoperative diagnosis]. / Klinische Uberprüfung des Tumormarkers CA 19-9 im Vergleich zum karzinoembryonalen Antigen (CEA) in der chirurgischen prä- und postoperativen Diagnostik.

A new tumor marker (CA 19-9) was investigated. CA 19-9 is a tumor-associated antigen which is detected by a monoclonal antibody. CA 19-9 (CIS-Centocor) was compared simultaneously with CEA (carcinoembryonic antigen) in 347 patients. 123 patients with gastrointestinal tumors showed a sensitivity of 31% for CA 19-9 (CEA 49%), combination increased sensitivity to 58%. The highest sensitivity was found in pancreas carcinoma (CA 19-9 75%, CEA 66%, combination 92%); it was lower in gastric, colon, and oesophagus carcinomas. In relapsed colorectal carcinomas sensitivity was 53% (CEA 78%, combination 85%). In cases of relapse, tumor markers may become positive even if they were not detectable before resection of the primary tumor. Specificity for CA 19-9 was 100% (CEA 84%) compared to a group of non-malignant diseases including patients with inflammations and patients with nicotin abuse (n = 102). Because of its high specificity and superior sensitivity to CEA in pancreas carcinomas CA 19-9 should be determined in primary and relapse diagnosis in combination with CEA.