Full Clinical Remission Research Articles

Low growth hormone response to growth hormone–releasing hormone in child depression

Background: This study examined growth hormone (GH) response to growth hormone–releasing hormone (GHRH) in a large sample of depressed children compared with normal control children. Within-subject comparisons were also performed in control subjects to examine test–retest reliability and in depressed children comparing episode versus clinical recovery. Methods: The sample included depressed children ( n = 82) and normal control children ( n = 55) group-matched for age, gender, and pubertal status; the mean ages were 11.2 ± 1.7 and 11.2 ± 1.8 years, respectively. We gave GHRH (0.1 mcg/Kg) at 9 am, and serum GH levels were determined every 15 min from −30 min through +90 min of the GHRH infusion. A subgroup of normal control subjects ( n = 11) repeated the protocol for test–retest reliability within a 2-month interval. A subgroup of depressed children ( n = 20) were restudied off all medications following full clinical remission from depression. Results: The mean GH response to GHRH was significantly lower in the depressed group (8.7 ng/mL ± SEM 0.9) compared with normal control children [12.2 ng/mL ± SEM 1.3; t(135) = 2.59, p = .01 effect size 0.44]. The test–retest reliability of GH response to GHRH was stable (intraclass correlation = .93 for mean post-GH). The GH response to GHRH remained low in subjects restudied during clinical remission from depression. Conclusions: Depressed children show low GH response to GHRH. The measure appears to be reliable, and the low GH response continues following clinical remission. Further studies are needed to explore the mechanism and relative specificity of this finding.

CTLA-4-Fc treatment of ongoing EAE improves recovery, but has no effect upon relapse rate.: Implications for the mechanisms involved in disease perpetuation

Several laboratories including ours have shown that T cell co-stimulation mediated through B7-1 or B7-2 is critical to the initiation of EAE. The role of T cell co-stimulation in ongoing EAE is less clear. In the present study, 32 mice with established EAE were randomly assigned to receive treatment with either CTLA-4-Fc or control Ig. Mice were followed daily by clinical scoring for 2 months post-immunization. A significant improvement in the degree of recovery following the acute episode and following relapses of EAE was observed in those mice randomized to CTLA-4-Fc treatment. Full clinical remission occurred twice as often in the CTLA-4-Fc group as in those mice receiving placebo, whereas placebo-treated mice were more likely to develop a stable prolonged neurologic deficit. Serial clinical scoring revealed no effect of CTLA-4-Fc upon relapse rate, with greater than 80% of the mice in each group displaying at least one clinical EAE relapse. In that the activation of memory T cells is relatively independent of T cell co-stimulation, these results indicate that development of chronic disease is associated with the activation of naive T cells and the recruitment of the latter cells into the disease process. Blocking B7 molecules may be beneficial in the treatment of established CNS inflammatory demyelinating diseases such as multiple sclerosis.

The Munich Vulnerability Study of Affective Disorders. Overview of the results at index study

The neurobiological alterations commonly found in affective disorders (e.g., alterations in the nocturnal sleep profile, dysfunction of the hypothalamic-pituitary-adrenocortical system) gradually recover with improvement of the depressive syndrome. Their persistence during full clinical remission, however, is associated with an increased risk for relapse and, thus may represent trait markers for affective disorders. In order to test this hypothesis, we designed a prospective study in which healthy first-degree relatives (high-risk probands; HRPs; n = 54) of patients with an affective disorder are investigated by means of polysomnography, the combined dexamethasone and corticotropine-releasing hormone (DEX-CRH) test and a variety of psychometric scales. In the present part of the study (index assessment), these HRPs, as a group, showed depression-like alterations in both the sleep pattern and the DEX-CRH-test outcome; furthermore, their psychometric profile was characterized by elevated scores on the scales assessing "rigidity" and "autonomic lability". On a single-case level, 35% of the HRPs were identified as conspicuous (depression-like) in at least two of the three areas investigated. A decision of whether or not this "conspicuousness" indeed represents a trait marker for affective disorders can be reached when the follow-up part of the study has identified those HRPs with their respective premorbide status who have developed an affective disorder in the meantime.

Open-label, uncontrolled trial of bowel sterilization and repopulation with normal bowel flora for treatment of inflammatory bowel disease

In this open-label, uncontrolled study, six patients with inflammatory bowel disease (IBD) (2 with ulcerative colitis, 1 with collagenous colitis, 1 with Crohn's disease, and 2 with indeterminate type) were treated with bowel decontamination using mechanical cleansing and antibiotics followed by repopulation with 12 strains of colonic bacteria from normal donors. One patient relapsed after 13 months following treatment with an antibiotic for an upper respiratory infection. One patient remains in full clinical remission after 18 months, and another patient after 32 months; the other three patients' symptoms did not change with treatment. No evidence of toxicity from treatments was observed. None of the patients who were in remission required therapy for IBD.

Reciprocal changes in complement activity and immune-complex levels during plasma infusion in a C2-deficient SLE patient.

Although systemic lupus erythematosus (SLE) is abnormally common in individuals with complement deficiency, conclusive evidence has been lacking for a direct causal relationship between disease manifestations and a missing complement component. A patient with C2 deficiency and SLE has been treated with 56 courses of fresh frozen plasma (FFP) infusions over a period of 8 years. Each infusion, involving a total of 12 units of FFP administered in equal doses over 4 consecutive days, has consistently resulted in a transient restoration of the classical pathway of complement, and a full clinical remission lasting 6-8 weeks. This report is concerned with changes in the levels of immune complexes, C2 and C3d during an infusion cycle. Four progressively rising peaks in C2 and C3d were observed during the 4 days of the plasma infusion, and these peaks coincided with four reciprocally descending troughs in the levels of immune complexes. Identical fluctuations have been consistent in all the plasma-infusion cycles that have so far been monitored, and their consistent association with clinical remissions indicates a causal relationship between the C2 restoration and clinical remissions in this C2-deficient SLE patient.

Serum amyloid P component scintigraphy and turnover studies for diagnosis and quantitative monitoring of AA amyloidosis in juvenile rheumatoid arthritis.

To evaluate aspects of the natural history of AA amyloidosis complicating juvenile rheumatoid arthritis (JRA), and its response to therapy with chlorambucil. Scintigraphy and 7-day turnover studies were performed in JRA patients with histologically proven (n = 35) or clinically suspected (n = 30) AA amyloidosis, following intravenous injection of 123I and 125I-labeled serum amyloid P component (SAP). Prospective monitoring studies were performed over 2-3 years in 20 patients with amyloidosis. All but 2 amyloidosis patients were treated with chlorambucil. Positive scanning results were obtained in all patients in whom imaging was performed within 12 years of positive biopsy findings of amyloid and in 5 patients with clinically suspected amyloidosis. Negative scanning results with normal SAP metabolism, indicating regression of amyloid, were obtained in 4 patients whose amyloidosis had been in full clinical remission for more than 12 years. Prospective monitoring studies in patients whose JRA-associated inflammatory activity was in remission demonstrated regression of amyloid in 8 patients and no substantial changes in 8 others; however, in 4 further patients with active inflammation, there was accumulation of amyloid. There was a very poor correlation between the amount of amyloid present at a particular site and the resultant organ dysfunction. Radiolabeled SAP scintigraphy and turnover studies are useful complementary tools in the diagnosis, screening, and quantitative monitoring of type AA amyloidosis in JRA. The amyloid deposits may progress and/or regress at different rates in different anatomic sites over short periods.

Thymic involvement in Hodgkin disease: CT and sonographic findings.

To evaluate the morphologic characteristics and frequency of thymic enlargement in Hodgkin disease, the initial and follow-up computed tomographic (CT) scans of 43 patients with newly diagnosed Hodgkin lymphoma were retrospectively analyzed. Sonograms of the thymic region in 21 patients were also available and were compared with the CT scans. Initial CT scans showed thymic enlargement in 17 of the 43 patients, no evidence of thymic enlargement in 15 patients, and equivocal findings in 11 patients. Analysis of follow-up CT scans indicated that seven of the 11 patients with initially equivocal findings had had thymic enlargement. In all seven patients, the anterior mediastinal tumor shrank with therapy and adopted a typical tongue-shaped thymic configuration. In nine of the 24 patients with thymic enlargement, the thymus remained enlarged after therapy and full clinical remission. The comparison of sonograms and CT scans showed that sonography could not help differentiate the normal-size thymus from surrounding fatty tissue. All thymic glands that were considered diseased because of enlargement at CT were sonographically visible due to an abnormal, hypoechoic structure. The results of the study show that thymic enlargement presumed to be due to involvement by Hodgkin disease seems to occur more frequently than previously reported.

Increased Amounts of C4‐Containing Immune Complexes and Inefficient Activation of C3 and the Terminal Complement Pathway in a Patient with Homozygous C2 Deficiency and Systemic Lupus Erythematosus

Plasma and serum samples from a patient with homozygous C2 deficiency and severe systemic lupus erythematosus who responded with full clinical remission after plasma infusions were examined for immune complexes (IC), C3 activation products, and the terminal complement complex (TCC). Plasma contained large amounts of C4-containing IC but no C3-containing IC or complement activation products. Classical pathway activation in vitro did not lead to C3 activation or TCC formation as seen in normal serum, but a very efficient binding of C1q and C4 was found. No disturbances in alternative pathway activation were observed. The results indicate an impaired formation of C3-containing IC and an inefficient clearance of C4-containing IC, supporting the idea of a causal relationship between the dysfunctional classical pathway, pathophysiology, and clinical manifestations in this patient.

SUCCESSFUL PLASMA INFUSION TREATMENT OF A PATIENT WITH C2 DEFICIENCY AND SYSTEMIC LUPUS ERYTHEMATOSUS: CLINICAL EXPERIENCE OVER FORTY‐FIVE MONTHS

We describe a patient with C2 deficiency and severe systemic lupus erythematosus (SLE) that did not respond to conventional therapy. Over a period of 45 months, she was given 22 cycles of plasma therapy. For 6–8 weeks after each plasma infusion, there was a full clinical remission of the SLE, and a brief restoration of hemolytic complement activity. However, there were more prolonged increases in the activities of the complement components that are believed to be more directly involved in the clearance of immune complexes. Because of the theoretical risk that the infused complement might enhance inflammatory tissue damage, there has been some reluctance to try plasma replacement therapy in SLE patients with complement deficiency. We have not observed any adverse effects with the long‐term use of this treatment, and our experience indicates that this therapeutic approach can be beneficial.

Sleep EEG and nocturnal secretion of cortisol and growth hormone in male patients with endogenous depression before treatment and after recovery

The authors conducted a sleep-endocrine evaluation among 10 unmedicated male patients with major endogenous depression during their depressive episode and following full clinical remission and drug withdrawal. While abnormally high values for cortisol secretory activity normalized after return to euthymia, growth hormone release and characteristic disturbances of EEG sleep remained unchanged. Whether or not neuroendocrine and sleep EEG abnormalities, which are present in remission, are trait markers remains undecided until premorbid sleep-endocrine data are available.

The second-look operation in advanced ovarian cancer--experiences since the introduction of cisplatin combination chemotherapy

In cases of ovarian carcinoma the trend today is toward postoperative cytostatic follow-up therapy which is as aggressive as possible, though of limited duration. The aim is to achieve full clinical remission and to verify it histologically by a second-look-operation. This paper presents the results obtained in 41 women who underwent second-look surgery, out of a total of 87 women with advanced epithelial ovarian carcinoma (FIGO stage III and IV) who had been given combination chemotherapy with cisplatin postoperatively. Taking various well-known prognostic factors into account (stage, age, histologic grading, primary postoperative residual tumor mass), the situation before and after a second-look laparotomy was analyzed. The survival data (life table analyses according to Kaplan-Meier) indicate the importance of these prognostic factors. Approximately one-third of the patients had full clinical remission after aggressive cisplatin combination chemotherapy; complete remission was verified microscopically in 18% of all cases, with a mean of 12 biopsies. The long-term prognosis for such women, who can be cured even if they have primary advanced ovarian carcinoma, is likely to be good. In addition, present-day indications and the standard surgical procedure for a second-look operation are described.

Treatment of gram-negative folliculitis with isotretinoin.

The clinical and bacteriological findings are reported in 13 patients with gram-negative folliculitis before, during, and after treatment with isotretinoin (13-cis-retinoic acid). Patients were treated for 14-36 weeks with a daily dose of 0.5-1.5 mg isotretinoin/kg body weight. Inflammatory lesions were counted before and during weeks 2, 4, 8, 12, 16, 20, 24, 28, and 30 of therapy and again up to 172 weeks after cessation of treatment. In all patients there was an impressive improvement in clinical symptoms, especially a decrease in seborrhea and inflammatory lesions. Simultaneously, the gram-negative bacteria disappeared from the facial skin. Full clinical bacteriological remission was achieved in 9 patients within a period of up to 43 months, with minor recurrences of the disease in the remaining 4 patients.

Do true remissions in myasthenia really exist? An electrophysiological study

To answer the question whether true remissions in myasthenia gravis occurred, 20 patients were studied with a history of evident, typical myasthenia but in full clinical remission. Two control groups served as a comparison: one of 10 healthy volunteers and the other of 10 patients with generalized, presently active myasthenia. In 17 of the 20 patients in remission single-fibre EMG (SFEMG) abnormalities were found, indicating some subclinical disturbances of neuromuscular transmission (in 3 cases the results were overtly pathological, in 11 cases moderately pathological, and in 3 cases slightly pathological). The abnormalities found in the remission group were much less distinct than those in the group with clinically symptomatic myasthenia. A case illustrates these findings: a man in full remission following thymoma extirpation in whom the SFEMG revealed subclinical disturbances of the neuromuscular transmission. Three weeks later a full clinical relapse occurred. The results obtained suggest that in the majority of patients the remissions are only apparently complete. A pathological jitter in a patient in remission calls for special attention: the patient must be spared any immunological stimuli such as vaccination, injections of sera, infections etc.; no drugs can be given which may increase the neuromuscular block; an immunosuppressive course of treatment should be considered; prognosis should be reconsidered.

Twenty-four-hour serum levels of TSH in affective disorders.

As a part of a broad endocrine testing of patients with affective disorders the 24 h serum levels of thyrotropin (TSH) were investigated and correlated to the clinical history and disease symptoms. Thirty-two patients with the research diagnostic criteria of major depressive disorder were investigated. Twenty-six of these patients were reinvestigated in a state of full or partial clinical remission. Nine patients with unipolar and eight patients with bipolar affective disorders were also investigated in clinical remission. The control group comprised 32 healthy subjects. The results showed significantly lower 24 h serum levels of TSH and less variability of TSH levels during the 24 h period in the group with acute major depression compared with the controls. The 24 h serum levels of TSH normalized during clinical remission. Different subtypes of depression, different clusters of symptoms and severity of depression did not significantly correlate with the 24 h serum levels of TSH. There were also no significant correlations between abnormalities of the dexamethasone suppression test or nightly melatonin levels and the 24 h serum levels of TSH. The lower TSH levels seen in acute major depression could not be correlated to increased or decreased levels of peripheral thyroid hormones. The mechanism of the decreased 24 h serum levels of TSH is unclear. One possibility is an altered sensitivity in the thyrotrophs of the pituitary.

HLA system and therapy of psoriasis.

In 192 patients with psoriasis an increased frequency of the antigens HLA-B13 (19.79%, X2 = 32.79, p less than 0.001), HLA-B17 (24.47%, X2 = 64,84, p less than 0.001), and HLA-B27 (19.27%, X2 = 11.07, p less than 0.001) in comparison with the control group of 1,085 clinically healthy persons, was established. After 4 weeks of thalassotherapy 3 groups of patients could be distinguished: (1) those with full clinical remission - 50 (26.8%), (2) those with great or moderate improvement - 116 (60.4%), and (3) those with no improvement - 26 patients (13.6%). In the first two groups there is a statistically significant association with the HLA antigens B13 and B17. In the third group (no improvement) there is no such association with HLA-B13 (p less than 0.01). Consequently, patients in whom psoriasis is associated with HLA-B13 were better influenced by the thalassotherapy. The variability in the therapeutic efficiency means that perhaps there is a genetic heterogenicity in the group of common psoriasis.

Kombinierte Chemo- und Radiotherapie des lokalisierten und metastasierten Ewing-Sarkoms

Between 1973 and 1978 combined radiotherapy and chemotherapy were given to 22 patients with histologically proven Ewing's sarcoma. The combined chemotherapy consisted of cyclophosphamide, vincristin, adriamycin, as well as dacarbazine in some cases. The neoplasm was a localized one at the beginning of treatment in 14 of the 22. These patients received high-voltage radiotherapy to the primary focus at a focal dose between 42 and 55 Gray (4200-5500 rad), followed by chemotherapy. After 6--8 treatment cycles, adriamycin was replaced by methotrexate. Nine of the 14 patients survived without recurrence for 12 to over 59 months. Eight patients had extensive metastases at the beginning of treatment: they at first received only chemotherapy, followed by radiotherapy or operation, as indicated. Full clinical remission was achieved in five of them: in three this remission has now lasted for more than 18, 40 and 44 months, respectively. These results indicate that (1) additional chemotherapy improves the prognosis of localized Ewing's sarcoma, and (2) even in far-progressed cases the combination of chemotherapy and radiotherapy can achieve lasting remission, which may in fact be a true cure.

Chronic non-specific ulcerative duodenojejunoileitis: report of four cases.

Four patients with chronic non-specific ulcerative duodenojejunoileitis (CNSUDJI) are reported. The clinical picture included abdominal pain, fever, and a malabsorption syndrome. Main rediological findings were diffuse narrowing of the jejunal loops with total effacement of the mucosal folds. Multiple peroral biopsies of the small intestine showed various degrees of mucosal abnormalities from total villous atrophy to normal villi, but ulcerations were diagnosed only by operative full thickness biopsies or resection of the small bowel. The ulcerative process was associated with well-documented coeliac disease in two patients: in one of them it occurred as a fatal complication involving also the colon, three years after the start of a gluten free diet, while the disease was in full clinical and histological remission. In the other case, coeliac disease was revealed by obstructive symptoms due to stenosing ulcerations; five months after surgical resection of the stenosis, institution of a gluten free diet induced a dramatic improvement. In the two other patients ulcerations were not associated with coeliac disease: one of them had a patchy villous atrophy and resisted a gluten free diet and total parenteral nutrition; she was improved by and dependent upon steroids but finally died. The last patient had normal villous height; ulcerations were located exclusively along the mesenteric border of the small bowel; he had a low-grade protracted evolution resisting any form of therapy and developed a peripheral neuropathy of unknown aetiology. On the basis of our cases and of a review of the literature the discussion focuses on the difficulty in diagnosing CNSUDJI, its relationship with coeliac disease, and its management and prognosis.

Systemic Lupus Erythematosus With a Protein-Losing Enteropathy

Anasarca with pronounced hypoalbuminemia developed in a young woman 15 months after the onset of a mild, arthralgic type of systemic lupus erythematosus (SLE) without evidence of active nephritis. Investigation indicated a gastrointestinal rather than a renal site for protein loss. A full clinical remission was achieved with low-dose corticosteroid therapy.

The augmented insulin tolerance test for detecting insulin resistance.

SUMMARY 1. An augmented insulin tolerance test and its normal response is described; after a standard preparation, 11·1 u. of soluble insulin/m.2 of body surface is injected intravenously, and the level of blood sugar followed for 2 hr. 2. The degree of insulin resistance, in such states as acromegaly, can be indexed by the sum of the blood sugar values, as mg./100 ml., at 60, 90 and 120 min. after insulin. In normal subjects the mean 'insulin resistance index' was 92 (range 62–142). The test is valid only if the fasting blood sugar is normal. 3. Results are reported in: (a) twelve 'untreated' acromegalics in all of whom the test showed an abnormal insulin resistance index (mean 173 and range 144–228); (b) fourteen treated acromegalics (after gold-198 or yttrium-90 implants), in eight of whom the insulin resistance index was normal, although only five were judged to be in full clinical remission; (c) twelve subjects with gross but 'simple' obesity in whom the test results were nearly as abnormal as those of the 'untreated' acromegalics (mean insulin resistance index 159 and range 119–221). 4. The test can be used to assess the 'activity' of acromegaly and its response to treatment, provided the subject is not also grossly obese.