Clinical and biochemical response to neridronate treatment in a patient with osteoporosis-pseudoglioma syndrome (OPPG).

Osteoporosis-pseudoglioma syndrome (OPPG) is a rare autosomal recessive syndrome characterized by juvenile-onset osteoporosis and ocular abnormalities due to a low-density lipoprotein receptor-related protein 5 (LRP5) gene mutation. Treatment with bisphosphonates, particularly with pamidronate and risedronate, has been reported to be of some efficacy in this condition. We report on a patient with OPPG due to an LRP5 gene mutation, who showed an encouraging response after a 36-month period of neridronate therapy. We report a case of a patient treated with bisphosphonates. Bisphosphonates should be administered in OPPG patients as a first-line therapy during early childhood.

Serum creatine kinase isoenzymes in children with osteogenesis imperfecta.

This study evaluates serum creatine kinase isoenzyme activity in children with osteogenesis imperfecta to determine its usefulness as a biochemical marker during treatment with bisphosphonate. The changes of creatine kinase (CK) isoenzyme activity during and after discontinuation therapy were observed. These results could be useful in addressing over-treatment risk prevention. INTRODUCTION: The brain isoenzyme of creatine kinase (CKbb) is highly expressed in mature osteoclasts during osteoclastogenesis, thus plays an important role in bone resorption. We previously identified high serum CKbb levels in 18 children with osteogenesis imperfect (OI) type 1 treated for 1 year with bisphosphonate (neridronate). In the present study, serum CK isoenzymes were evaluated in the same children with continuous versus discontinued neridronate treatment over a further 2-year follow-up period. METHODS: This study included 18 children with OI type 1, 12 with continued (group A) and 6 with ceased (group B) neridronate treatment. Auxological data, serum biochemical markers of bone metabolism, bone mineral density z-score, and serum total CK and isoenzyme activities were determined in both groups. RESULTS: Serum CKbb was progressively and significantly increased in group A (p < 0.004) but rapidly decreased to undetectable levels in group B. In both groups, the cardiac muscle creatine kinase isoenzyme (CKmb) showed a marked decrease, while serum C-terminal telopeptide (CTx) levels were almost unchanged. CONCLUSIONS: This study provides evidence of the cumulative effect of neridronate administration in increasing serum CKbb levels and the reversible effect after its discontinuation. This approach could be employed for verifying the usefulness of serum CKbb as a biochemical marker in patients receiving prolonged bisphosphonate treatment. Moreover, the decreased serum CKmb levels suggest a systemic effect of these drugs.

Altered collagen I and premature pulmonary embryonic differentiation in patients with OI type II.

Pulmonary hypoplasia and respiratory failure are primary causes of death in patients with osteogenesis imperfecta (OI) type II. OI is a genetic skeletal disorder caused by pathogenic variants in genes encoding collagen type I. It is still unknown if the collagen defect also affects lung development and structure, causing lung hypoplasia in OI type II. The aim of this study was to investigate the intrinsic characteristics of OI embryonic lung parenchyma and to determine whether altered collagen type I may compromise airway development and lung structure. Lung tissue from nine fetuses with OI type II and six control fetuses, matched by gestational age, was analyzed for TTF-1 and collagen type I expression by immunohistochemistry, to evaluate the state of lung development and amount of collagen. The differentiation of epithelium into type 2 pneumocytes during embryonic development was premature in OI type II fetuses compared to controls (p < 0.05). Collagen type I showed no significant differences between the two groups. However, the amount of alpha2(I) chains was higher in fetuses with OI and the ratio of alpha1(I) to alpha2(I) lower in OI compared to controls. Cell differentiation during lung embryonic development in patients with OI type II is premature and impaired. This may be the underlying cause of pulmonary hypoplasia. Altered cell differentiation can be secondary to mechanical chest factors or a consequence of disrupted type I collagen synthesis. Our findings suggest that collagen type I is a biochemical regulator of pulmonary cell differentiation, influencing lung development.

Ultrastructure study of skin fibroblasts in patients with Ehlers-Danlos Syndrome (EDS): preliminary results.

AIM OF THE STUDY: To investigate, in vivo and in vitro, the fibroblast-to-myofibroblast transition in patients with hypermobile Ehlers-Danlos Syndrome (EDS). To analyze the dermis of patients with classical form of EDS (cEDS) and with hEDS, to identify qualitative and/or quantitative differences in ECM component and ultrastructural changes in collagen. MATERIALS AND METHODS: Seven subjects, aged over 18, two with cEDS and five with hEDS underwent two skin biopsy. One sample was prepared for transmission electron microscopy (TEM), the other for immunofluorescence. The diameter of collagen fibers was measured with TEM. Fibrils were analyzed in four patients: the two with cEDS and two with hEDS. For each patient, the diameter of n=250 collagen fibrils was measured. αSMA was used as specific marker for myofibroblast to highlight their presence in vivo in the skin of patients with hEDS. RESULT: IF observation could not assess an increased expression of αSMA in hEDS patients, which showed no statistical difference compared to classic form patients. The major result from the analysis of TEM images is the clear difference in ECM composition between the two forms of EDS: ECM in hEDS is optically more dense and more prominently composed of elastic fibers. CONCLUSION: Our study provides the following important evidence: 1) the absence in vivo of dermal fibroblasts in patients with hEDS, demonstrated by αSMA negativity; 2) the presence of statistically significant changes in the diameter of collagen fibrils between the classic and the hypermobile forms.

Transplant of the teres major in the treatment of irreparable injuries of the rotator cuff (long-term analysis of results).

Purpose of this study is to evaluate the effectiveness of muscle transfer of the teres major in the treatment of irreparable posterosuperior injuries of the rotator cuff. Long-term monitoring of the results obtained in 20 patients treated at our clinic using this method are reported, comparing the data obtained in evaluations of results with preoperative values. Clinical evaluations were obtained using the Constant Score System, while X-ray examination showed the presence of osteoarticular modifications, and MRI and electromyography the preserved morphology and function of transplant. The mean Constant Score increased from 31.6 points preoperatively to 66.1 points postoperatively at the time of follow-up. At follow-up, MRI allowed us to evaluate any fatty degeneration of the muscle fibers of transfer and the integrity of tendinous insertion on the humeral greater tuberosity. The obtained results allowed us to reveal the advantages and the disadvantages of teres major transplant in irreparable posterosuperior ruptures of the cuff.

Unsuccessful cimetidine treatment of peptic ulcer: analysis of the factors involved.

Healing rates were examined retrospectively in 124 outpatients with peptic ulcer who had received cimetidine for at least four weeks. Treatment was unsuccessful in 73 patients. A statistical analysis of the factors involved in treatment failure revealed that in patients with duodenal ulcers 60.6% of the treatment successes versus 26.8% of the treatment failures were nonsmokers (P less than 0.001). There was a significantly higher (P less than 0.01) incidence of varioliform gastritis among treatment failures (19.2%) than treatment successes (3.9%). The following factors seemed to have no influence on rates of ulcer healing: age, sex, duration of ulcer disease, duration (beyond four weeks) of cimetidine therapy, family history of peptic ulcer, alcohol consumption, and coffee consumption. Although there was a higher gastric:duodenal ulcer ratio as well as higher consumption of anti-inflammatory drugs in treatment failures than in treatment successes, the difference was not statistically significant.

Transfer of sensory nerves in hand surgery.

The transfer of sensitive dorsal rami of the ulnar nerve (two cases) and of two sensitive dorsal rami of the radial nerve (five cases) was accomplished in order to restore the sensitivity of the first three finger tips in patients suffering from serious and longstanding inveterate lesions of the median nerve. The Authors describe the two surgical techniques in detail and, according to the satisfactory results obtained, specify the indications and advantages of this operation.

Immediate hypersensitivity gastropathy and duodenogastric reflux.

The purpose of the present study was to define a correlation between immediate hypersensitivity gastropathy and duodenogastric reflux. The gastric mucosa can often be involved in immediate hypersensitivity reactions, mainly in atopic subjects suffering from other allergic diseases. The typical endoscopic findings concern alterations of the gastric mucosa, like pomphi and variolae, and alterations of the gastric motility, like spasms and pyloric disturbances, all of them occurring in the antrum in most cases. Histology and immunofluorescence show peculiar patterns. Bile reflux is present in over 50% of these patients. The possible relationship between duodeno-gastric reflux and the gastric hypersensitivity reactions is briefly discussed in the light of what is known about the action of bile on the gastric barrier.