Specific Small-intestinal Lactase Deficiency in Adults

LTT and/or small intestinal biopsy with disaccharidase activity assay was performed in 700 out of 1,300 adult patients at two gastroenterological units. Of 18 patients with specific lactase deficiency only 4 had a history of a previous acute gastrointestinal disease. 17 patients had apparent clinical symptoms, but only 8 had spontaneously observed relation between symptoms and milk intake. In many patients small amounts of milk were sufficient to provoke symptoms, and although dietary treatment was successful, rigorous exclusion of lactose was sometimes necessary.     

Increased Serum Osteocalcin Levels in Patients with Lactase Deficiency

Serum levels of osteocalcin, a noncollagenous bone matrix protein, have been found to be a specific biochemical parameter of bone formation. In the literature in subjects with osteoporosis, an increased incidence of lactase deficiency has been described. We therefore determined the serum levels of osteocalcin in 10 patients with lactase deficiency and in 20 control subjects by radioimmunoassay. The patients with lactase deficiency were dietary treated and had a very low daily calcium intake. Serum osteocalcin levels were significantly higher in the patients with lactase deficiency than in the control subjects. In contrast, serum levels of parathyroid hormone, alkaline phosphatase, calcium, and phosphorus were not statistically different in the two groups. Our data suggest an increased rate of bone turnover in patients with lactase deficiency on a low calcium diet; possibly calcium supplementation is indicated in dietary-treated patients with lactase deficiency.     

Long-Term Efficacy and Safety of Somatropin for Adult Growth Hormone Deficiency

The beneficial effects of somatropin (growth hormone [GH] replacement therapy) in adults are now established. Long-term somatropin administration in GH-deficient adults improves body composition, muscle strength, quality of life, bone mass and density, and lipoprotein pattern. The extent to which somatropin therapy can also reduce cardiovascular morbidity and mortality in GH-deficient adults remains to be determined. By starting with a low dose of somatropin, which is gradually increased based on clinical response (body composition, well-being, and serum insulin-like growth factor-1 concentration), effective treatment can be achieved with a minimum of fluid-related adverse effects. Thorough long-term monitoring of glucose metabolism, cardiovascular measurements, and underlying pituitary disease, is, however, mandatory.     

T-Lymphocyte Deficiency Following Adult Thymectomy in Man

10 patients thymectomized about 20 years earlier were tested for delayed skin reactivity against mumps, streptokinase-streptodornase and PPD antigens. Their T and B lymphocytes in peripheral blood were determined. 6 patients were surgically thymectomized and 2 of them received postoperative irradiation. 4 patients were treated with only high dose irradiation to the mediastinal compartment. None of the patients responded to all skin antigens, 1 was positive to two antigens and 3 to one antigen. The remaining patients were non-responders. The number of peripheral blood lymphocytes was slightly decreased in the patients. A significant decrease in the number of T-lymphocytes (p < 0.005) was found in the whole patient group, and the depression was more pronounced in the surgically thymectomized patients (p < 0.001). The number of B-lymphocytes was unaltered. It is concluded that the abnormalities in this patient group reflect a T-lymphocyte deficiency. The immunologic status of the patients before treatment is not known. However, in 3 patients with recently discovered untreated thymomas no abnormalities were found. Thus, adult thymectomy in man seem to lead to deficiency of cell mediated immunity, indicating an influence of the thymus in immunological functions during adult life.     

Primary Leucocyte Alkaline Phosphatase Deficiency in an Adult with Repeated Infections

SUMMARY. An individual with repeated bacterial infections, eczema, hyperimmuno-globulin E, and a primary deficiency of leucocyte alkaline phosphatase is described. The LAP-deficient neutrophils from this patient had marginally deficient bactericidal activity particularly when challenged with high ratios of bacteria per neutrophil. Leucotactic, metabolic and morphologic features of the neutrophils from the patient were normal. Evidence is presented which contrasts this patient's condition with previously described primary or secondary deficiencies of LAP.     

Visual Hallucinations in a Patient with Adult Onset Acid Maltase Deficiency Disorder

A 66-year-old male presented with visual hallucinations. He had chronically elevated serum creatine kinase (CK) levels without muscle weakness. His hospital course was complicated by hypercapnic respiratory failure requiring mechanical ventilation. His hallucinations completely subsided on mechanical ventilation. Elevated CK levels prompted a muscle biopsy, which showed myopathy consistent with acid maltase deficiency disorder (AMDD). This is the first reported case of adult onset AMDD presenting with psychiatric symptoms. Our objective in reporting this case is to encourage early recognition of neuromuscular respiratory failure in AMDD and to reinforce that respiratory failure may develop without associated extremity muscle weakness.     

Hypopituitarism and Growth Hormone Deficiency in Adult Subjects after Traumatic Brain Injury: Who and When to Test

Traumatic brain injury (TBI) was traditionally considered an infrequent cause of hypopituitarism. However recent reports strongly suggest that TBI-mediated pituitary hormones deficiency may well be more frequent than previously thought. As the prevalence of hypopituitarism is not dependent on the severity of the trauma and considering the high number of TBI events in all industrialized countries a screening procedure for detecting hormone deficiencies in all TBI patients is not possible. In the present work a suggestion for screening a subgroup of TBI patients is discussed in order to increase the effectiveness of the whole procedure.     

Discontinuing Long-Term GH Replacement Therapy--A Randomized, Placebo-Controlled Crossover Trial in Adult GH Deficiency

Context: Adult GH deficiency (GHD) is associated with impaired quality of life (QoL) and increased cardiovascular risk. Continued long-term efficacy in terms of QoL and cardiovascular risk factors has been indicated in open surveillance studies. Objectives: The aim was to study the impact of discontinuation of long-term GH replacement on QoL, body composition, and metabolism. Design and Setting: We conducted a randomized, double-blind, placebo-controlled 4-month crossover trial in a referral center. Patients: Sixty adult hypopituitary patients with GHD and more than 3 yr of continuous GH replacement therapy (mean treatment duration, 10 yr) participated in the study. Intervention: Patients received GH or placebo. Main Outcome Measurements: We measured QoL using validated questionnaires; body composition using computer tomography, dual-energy x-ray absorptiometry, and bioelectrical impedance spectroscopy; and insulin sensitivity using the short insulin tolerance test. Results: Mean serum IGF-I decreased from 168 ± 52 to 98 ± 47 μg/liter during the placebo period (P < 0.001). Two QoL domains (emotional reactions and positive well-being) in the Nottingham Health Profile and Psychological General Well-Being questionnaires deteriorated during placebo, compared with GH treatment (P < 0.05). Waist circumference and sc and visceral fat mass increased, and extracellular water and muscle area decreased during the placebo period (all P < 0.05). C-reactive protein and total-, low-density lipoprotein-, and high-density lipoprotein-cholesterol increased, and insulin sensitivity improved during placebo, compared to GH treatment (P < 0.05). Conclusion: After more than 3 yr of GH replacement therapy, a 4-month period of placebo treatment caused self-perceived deterioration in QoL and increased abdominal fat accumulation. Moreover, markers of systemic inflammation and lipid status deteriorated, whereas insulin sensitivity improved. Long-term continuous GH replacement is needed to maintain therapeutic effects of GH on QoL and cardiovascular risk factors.     

Efficacy of Addition of Antiangiogenic Agents to Taxanes-Containing Chemotherapy in Advanced Nonsmall-Cell Lung Cancer: A Meta-Analysis and Systemic Review

Preclinical researches indicated a potential synergistic effect of taxanes-containing chemotherapy (TCC) and antiangiogenic agents (AAs) on the treatment of advanced nonsmall-cell lung cancer (NSCLC). The advantage of adding AA to TCC in the real world remains confusing. We summarized the current evidences from relevant phase II/III randomized controlled trials (RCTs) by performing this meta-analyses.Electronic databases were searched for eligible literatures. The primary endpoint was overall survival (OS). Pooled hazard ratios (HRs) and 95% confidence intervals (CIs) for outcomes were calculated using RevMan 5.2.A total of 14 phase II/III RCTs involving 9703 participants were included. Compared to standard TCC, the addition of AA was associated with the significant better OS (HR 0.92, 95% CI 0.87–0.97, P = 0.002), prolonged progression-free survival (HR 0.79, 95% CI 0.71–0.87, P < 0.00001), superior response rate (risk ratio [RR] 1.69, 95% CI 1.47–1.95, P < 0.0001), and disease control rate (RR 1.19, 95% CI 1.08–1.32, P < 0.00001). Subgroup analyses indicated that patient treated with monoclonal antibodies (HR 0.89, 95% CI 0.82–0.96, P = 0.02) as well as application in second-line (HR 0.91, 95% CI 0.85–0.96, P = 0.02) acquired significant OS improvement. Other clinical factors directing significant OS improvement by the combination strategy included nonsquamous cancer (P = 0.002), nonsmokers (P = 0.0005), and female (P = 0.02). Toxicities were greater but generally mild or moderate in the combination group, and were mostly manageable.In summary, the addition of AAs to TCC could improve prognosis of advanced NSCLC. Furthermore, proper selection of patient population and AAs is crucial for clinical trials design and clinical practice in the future.     

Spontaneous Gonadotrophin Deficiency Recovery in an Adult Patient with Langerhans Cell Histiocytosis (LCH)

Langerhans cell histocytosis (LCH) is a rare disease which exhibits a particular predilection for pituitary involvement leading to diabetes insipidus (DI) and other anterior pituitary hormonal deficiencies that are usually permanent and unresponsive to treatment. We report a 35 year old woman with a 10 year history of multisystemic LCH who developed DI, mild hyperprolactinemia, gonadotrophin and partial growth hormone deficiency following a normal delivery that was accompanied with infundibular thickening on pituitary magnetic resonance imaging (MRI). Following several courses of glucocorticoid administration, that were not associated with any substantial improvement, the patient was started on estrogen replacement therapy and cabergoline. After a three year period free of further relapses she developed irregular uterine bleeding. Following estrogen and cabergoline discontinuation she resumed normal menstruation while a repeated MRI of the pituitary showed an almost normal infundibulum. Endocrine investigation revealed normal gonadotrophin axis and prolactin levels, while the patient continues to menstruate, every 30–40 days, ten months after the resumption of her menstrual cycle. This case demonstrates for the first time that LCH induced pituitary deficiencies can run a variable clinical course and even spontaneously recover.     

Efficacy and Tolerability of Budesonide Clickhaler® and Turbuhaler® in Adult Asthma

New dry powder inhalers should be clinically comparable with established devices to ensure the continuity of effective therapy for asthma patients. This randomized, open, parallel group study compared the clinical efficacy and tolerability of budesonide delivered via Clickhaler® or Turbuhaler® dry powder inhalers in adults with mild to moderate stable asthma. Following a 4-week stabilizing period using budesonide Turbuhaler adults aged 18 years or older, who had been treated with inhaled corticosteroids for at least the previous 12 weeks, were randomized to receive budesonide twice daily (≤ 1600 µg/day) via either Clickhaler (n = 110) or Turbuhaler (n = 112) for 12 weeks. Morning peak expiratory flow (PEF), evening PEF, asthma symptoms, and use of inhaled short-acting β₂-agonist were recorded daily by the patients on diary cards. Lung function and tolerability data were recorded at clinic visits following 4, 8, and 12 weeks' treatment. Efficacy was measured primarily by mean change from the run-in baseline in weekly morning PEF. Of the 222 patients randomized to treatment, 167 completed the study according to the protocol. Repeated-measures analysis of covariance indicated that the devices were clinically equivalent; a treatment difference of ? 2.3 L/min separated the group mean changes in weekly morning PEF (95% confidence interval ? 7.9 to 3.3). Secondary analyses also supported clinical comparability. This study demonstrates the comparable clinical efficacy and tolerability of budesonide Clickhaler and Turbuhaler devices in adult patients with stable asthma.     

Efficacy and Tolerability of Budesonide Clickhaler® and Turbuhaler® in Adult Asthma

New dry powder inhalers should be clinically comparable with established devices to ensure the continuity of effective therapy for asthma patients. This randomized, open, parallel group study compared the clinical efficacy and tolerability of budesonide delivered via Clickhaler® or Turbuhaler® dry powder inhalers in adults with mild to moderate stable asthma. Following a 4-week stabilizing period using budesonide Turbuhaler adults aged 18 years or older, who had been treated with inhaled corticosteroids for at least the previous 12 weeks, were randomized to receive budesonide twice daily (≤ 1600 µg/day) via either Clickhaler (n = 110) or Turbuhaler (n = 112) for 12 weeks. Morning peak expiratory flow (PEF), evening PEF, asthma symptoms, and use of inhaled short-acting β₂-agonist were recorded daily by the patients on diary cards. Lung function and tolerability data were recorded at clinic visits following 4, 8, and 12 weeks' treatment. Efficacy was measured primarily by mean change from the run-in baseline in weekly morning PEF. Of the 222 patients randomized to treatment, 167 completed the study according to the protocol. Repeated-measures analysis of covariance indicated that the devices were clinically equivalent; a treatment difference of - 2.3 L/min separated the group mean changes in weekly morning PEF (95% confidence interval - 7.9 to 3.3). Secondary analyses also supported clinical comparability. This study demonstrates the comparable clinical efficacy and tolerability of budesonide Clickhaler and Turbuhaler devices in adult patients with stable asthma.     

脾虚三证模型大鼠脂质过氧化损伤的比较

探讨实验性脾虚大鼠脂质过氧化损伤的差异性。方法采用饮食加劳倦等复合因素分别复制脾虚不同证型动物模型。观察各模型组和治疗组的脂质过氧化物(LPO)的含量和谷胱甘肽过氧化物酶(GSH-Px)、超氧化物岐化酶(SOD)、心肌黄酶(DTD)的活性变化。结果各脾虚模型大鼠LPO呈不同程度升高,各种抗氧化酶活性不同程度下降,且组间差异显著。各治疗组药物具有降低LPO、升高抗氧化酶活性的作用。结论脂质过氧化损伤是脾虚三证的共同病理生理基础。     

脾虚三证模型大鼠脂质过氧化损伤的比较

目的 :探讨实验性脾虚大鼠脂质过氧化损伤的差异性。方法 :采用饮食加劳倦等复合因素分别复制脾虚不同证型动物模型。观察各模型组和治疗组的脂质过氧化物 (L PO)的含量和谷胱甘肽过氧化物酶 (GSH- Px)、超氧化物岐化酶 (SOD)、心肌黄酶 (DTD)的活性变化。结果 :各脾虚模型大鼠 L PO呈不同程度升高 ,各种抗氧化酶活性不同程度下降 ,且组间差异显著。各治疗组药物具有降低 L PO、升高抗氧化酶活性的作用。结论 :脂质过氧化损伤是脾虚三证的共同病理生理基础。