Skeletal development and bone functional adaptation.

The role of in vivo mechanical loading histories in normal skeletogenesis is related to the process of adaptive, stress-regulated bone remodeling in the adult. The results of many previous computer models for endochondral ossification and bone modeling and remodeling are reviewed. These studies support the view that simple stress-related mathematical algorithms or "construction rules" can be used to emulate normal skeletal development and architectural construction. Such mathematical rules presumably represent the net result of biophysical phenomena influencing cell metabolism and biosynthetic activity. These rules are also successful in describing the adaptation of adult bone to changes in tissue stresses. The findings suggest that stress-related functional adaptation in mature bones may be merely the adult manifestation of the same mechanical construction rules that guide and constrain normal development.


Mechanical stress and osteogenesis in vitro.

The use of hydrostatic pressure to apply mechanical stress to bone organ cultures is reviewed. Ossifying long bones and calvarial rudiments are sensitive to this type of stress. Intermittent hydrostatic compression of near physiologic magnitude (ICF) has anabolic effects on mineral metabolism in such rudiments, and continuous hydrostatic stress of high magnitude (CCP) has catabolic effects. The effects of ICF may be ascribed to shear stress generated at tissue interphases of different chemical and mechanical properties. Local factors, such as prostaglandins and growth factors, seem to be involved in the tissue response to mechanical stress.


Control of bone architecture by functional load bearing.

The continuing ability of the skeleton to withstand functional loads without damage requires that bone mass and architecture are adjusted according to the loads experienced. Load bearing is the only functional influence that requires a particular bone architecture, and functionally engendered strains within the bone tissue provide the only feedback containing the necessary information on the relationship between current architecture and prevailing load history. The specific strain-related objectives of the adaptive modeling and remodeling response to load bearing have not been adequately defined. They appear to be different for cortical and cancellous bone and vary according to cortical location. Experiments suggest that adaptive modeling and remodeling is sensitive to dynamic but not static strain change and that the osteogenic response to a period of dynamic strain is quickly saturated but is higher when the rate of change in strain is high and the distribution of strain unusual. Presumably it is the cumulative effect of this osteogenic response to load bearing that normally maintains bone mass above that seen in disuse situations. Through their independent effects on bone cell behavior, nutritional and hormonal factors can enable, enhance, limit, or frustrate full expression of the osteogenic response to strain change. However, such systemic factors do not appear to be able to engender or successfully imitate the sustained cumulative local response to load bearing that normally maintains functionally appropriate bone mass and architecture. Experiments in vivo and in vitro suggest that in osteocytes and surface osteoblasts the almost immediate response to strain change is increased production of prostacyclin. Surface osteoblasts also produce prostaglandin E.(ABSTRACT TRUNCATED AT 250 WORDS)


Effect of intermittent mechanical force on bone tissue in vitro: preliminary results.

The structure of metatarsal bones from 18-day-old rats subjected to intermittent mechanical force in organ culture are reported. The application of mechanical force enhances the osteoid thickness and osteoblast number in the periosteum and increases the number of viable osteocytes. These results indicate that (1) the mature bone tissue survives in organ cultures; (2) the mechanical forces better preserve the structure of the osteocytes and stimulate the osteoblasts, and (3) stimulate the osteogenesis.


Demonstration of subchondral bone density patterns by three-dimensional CT osteoabsorptiometry as a noninvasive method for in vivo assessment of individual long-term stresses in joints.

Since the work of Pauwels and his successors, it has been possible to use the distribution of subchondral bone density within a joint surface as a metric parameter that can reflect the principal long-term stress acting upon a joint. However, the x-ray densitometry method he employed cannot be applied to living people. A procedure was therefore developed whereby CT osteoabsorptiometry (CT OAM), based on the use of computed tomography, allows the distribution pattern of the density to be demonstrated in living subjects. This method has now been further developed, so that the form of the individual joint surfaces can be included by means of a three-dimensional reconstruction program. This method is presented here. In addition, selected representative examples of various joints from normal people, athletes, and patients are used to demonstrate the use of CT OAM. In these examples from living subjects, regularly occurring, reproducible distribution patterns of subchondral bone density can be recorded, reflecting changes in mechanical stresses on a joint (increased stress, reduced stress, and disorders of joint mechanics). CT osteoabsorptiometry is demonstrated as a suitable noninvasive technique for investigating the individual long-term stresses (loading history) acting on a living joint.


Quantitative study of articular cartilage and subchondral bone remodeling in the knee joint of dogs after strenuous running training.

All tissues of the joint are affected in some way in osteoarthritis because the joint is an interactively functioning unit. Our goal was to investigate the combined responses of articular cartilage and subchondral bone to altered loading conditions to improve our understanding of the physiology of these two components and, ultimately, the pathophysiology of osteoarthritis. A group of 20 female beagle dogs were divided pairwise into runners (n = 10) and controls (n = 10). The running training on a treadmill started at the age of 15 weeks, and during the following 40 weeks the running distance was gradually increased to 40 km/day with a 15 degree uphill inclination. With this daily running distance the beagles ran another 15 weeks. The samples for histology were taken from 11 different locations of the knee joint. Subchondral bone and articular cartilage histomorphometry was carried out in three different regions of the specimens (central, middle, and peripheral regions) using an image-analyzing system and an eyepiece graticule. In all regions of the articular cartilage, both the uncalcified and calcified cartilage showed slightly increased thickness in the runner dogs. The change was more evident in the peripheral and the central areas. The thickness of the subchondral bone plate tended to be higher in runners, too. Bone histomorphometric parameters showed significant signs of increased remodeling. The most notable change was the enlargement of the bone formation surface. The most intense remodeling was usually observed either centrally or peripherally in the articular surface. The strongest increase in trabecular bone volume and thickness of the cartilage was recorded in the femoropatellar area.(ABSTRACT TRUNCATED AT 250 WORDS)


Does immobilization influence the systemic acceleratory phenomenon that accompanies local bone repair?

The rate of remodeling in the region of a bone defect exceeds normal tissue activity. It was Frost who described this reaction as the regional acceleratory phenomenon (RAP). We previously showed that restoration of a local bone defect in the rat leads not only to RAP but also leads to a systemic acceleration of osteogenesis (systemic acceleratory phenomenon, SAP) in distant sites of the skeleton. In this study we investigated the impact of immobilization of the defect-bearing extremity on the development of SAP. A hole 1.2 mm in diameter was drilled in the diaphysis of the left tibia of female rats. In the experimental group (n = 15), a knee tenotomy was performed in the defect-bearing left hind leg. We examined both femora, both tibiae, and the fourth lumbar vertebra by computed x-ray densitometry on day 7 postoperatively. Immobilization of the defect-bearing limb led to a decrease in x-ray density not only of the immobilized (p < 0.0001) but also of the contralateral tibia (p < 0.0001). Both femora (p < 0.001) and the fourth lumbar vertebra (p < 0.025) of the experimental group also showed a significant decrease in x-ray density. We previously showed that SAP leads to an increase in x-ray density of both femora. This increase is no longer detectable in animals after immobilization of the defect-bearing limb. Thus we conclude that immobilization interferes with SAP. This suggests the possible dependence of SAP on mechanical load. Furthermore, these data suggest a possible impact of local immobilization on the rest of the skeleton.


Mineral apposition rate in rat cortical bone: physiologic differences in different sites of the same tibia.

The mineral apposition rate (MAR) is a commonly used parameter for the characterization of bone formation and is often determined to test for experimental effects on cortical bone. We investigated whether there are physiologic variations in rat cortical MAR dependent on the side or site of measurement. In our experiment we used female rats. The animals were sacrificed on day 8, after double-fluorochrome labeling with calcein and tetracycline was performed. The MAR was calculated at 3.6, 5.4, 7.2, 9, and 10.8 mm from the epiphyseal growth plate of the lateral as well as of the medial endosteum of both right and left tibiae. We found a physiologic significant difference in the MAR between the lateral and the medial endosteal sites of the same tibia (p < 0.0001), especially near the epiphyseal growth plate. Regarding the same cortical side, there is a significant decrease (p < 0.0001) in the endosteal MAR with increasing distance from the epiphyseal growth plate. We conclude that the observed differences in endocortical MAR must be due to specific mechanical challenges. Because these differences are statistically significant, it is necessary to standardize the area of histomorphometric measurement not only with respect to the distance from the epiphyseal growth plate, but also with respect to the cortical side.


Interrelationships between geometric and mechanical properties of long bones from three rodent species with very different biomass: phylogenetic implications.

In femora from rats or mice, the area and moment of inertia (but not the wall-lumen ratio) of a diaphyseal section correlated with biomass and were determinants of the strength and stiffness of the integrated bone. In otter metacarpals, however, the geometric variable typically associated with body weight and mechanical ability of the integrated bone was the wall-lumen ratio (not the sectional moment of inertia). These differences may be associated with the meaningfulness of body density for natural selection in diving species like otters. A negative relationship between wall-lumen ratio and material modulus of elasticity in bones from the three species pointed out the impossibility of increasing diaphyseal thickness and stiffness at the same time. The results are compatible with the hypothesis that ecologic habits are selectively more important than phylogenetic relationships between species for the determination of bone mechanical properties in the upper vertebrates.


Effect of bone size, not density, on the stiffness of the proximal part of normal and osteoporotic human femora.

Proximal femur fractures in the elderly lead to a high rate of hospitalization. In studying the operative treatment of such fractures, it is first necessary to understand the relationship between the morphologic properties of this part of the femur (related to both geometry and density) and its mechanical properties. Numerous investigations showed that femoral strength correlates with bone mass; however, the dimension of the bones was not taken into account. We measured the relationship between the stiffness of the proximal femur under physiologic load and its geometry and density. Conventional x-rays and quantitative computed tomography (QCT) were carried out on pairs of human cadaver femora. Eight pairs were instrumented with strain gauges. Bones were subjected to an eccentric load that simulates moderate weight bearing (single-leg stance), and the strain parallel to the bone axis was plotted as a function of the load applied. An apparent bone stiffness was calculated as the ratio between the strain gradient within the section and the load applied. Strong correlation was found between x-ray densitometry and QCT. The bone stiffness also correlates strongly with the geometry (area) and slightly with bone mass; however, an unexpectedly low correlation was found between stiffness and density. We chose stiffness as a mechanical parameter (not strength) because it describes the "normal" bone behavior under load. Our results clearly demonstrate that the cross-sectional size of the bones must be taken into account when establishing the relationship between the mechanical characteristics of the bone and its morphology. In accordance with previous predictions, our results support that bone loss due to osteoporosis is compensated for by an increase in bone diameter.


Microgravity and bone adaptation at the tissue level.

Our knowledge of the adaptation of human bone microgravity remains poor despite long-term Russian spaceflights and the recent use of accurate techniques for bone mass measurements. The extent of bone deficits in the adaptation of the whole skeleton is not clear. At the tissue level, bone resorption and formation activities have been studied only in bones from rats after spaceflights lasting a few days to 3 weeks. In these animals, architectural features consistent with osteoporosis have been found in the proximal tibia. In pregnant animals the osteoclast population is increased at other skeletal sites. In areas of weight-bearing bones that are not protected by muscular insertions, bone resorption is not markedly altered after 7 days of spaceflight and bone formation is reduced. In areas of weight-bearing bones with muscular insertions and in non-weight-bearing bones, similar changes in bone cell activity are delayed. The severity of the response seems to vary with the location of the bone in the skeleton and its initial level of bone turnover. After 12.5 days the acute bone changes are less and no additional changes are observed after 21 days in space. We conclude that generalized bone deficits do not appear to be a consequence of microgravity but occur in localized areas according to the level of modeling and remodeling and of the support function of each bone at 1 g.


Effect of exercise and bisphosphonate on mineral balance and bone density during 360 day antiorthostatic hypokinesia.

As we enter a phase of space exploration that will involve long-duration flights, there is a need to use ground-based models to study the long-term effects of countermeasures to prevent the loss of bone mineral in microgravity. Mineral balances, hormone levels, and bone density were measured for 360 days in nine bed rest subjects treated with an exercise program used by cosmonauts. Four of these subjects received the bisphosphonate, ethane-1-hydroxy-1-disphosphonate, 900 mg daily, a drug known to inhibit bone resorption. Compared to a 120 day control period, the bisphosphonate combined with exercise reduced negative calcium balances by 50% for the first 120 days, 80% for the second 120 days, and 69% during the third 120 days. Exercise alone had no effect until the second 120 day period, when calcium balance improved 52%. Negative phosphorus balances were not affected by either treatment. Magnesium balances were negative during the first 120 days and returned to nearly normal during the last 240 days in both groups. The combined exercise and bisphosphonate treatment prevented increases in serum ionized calcium and decreases in plasma calcitonin during the first 120 days, as well as trends toward decreases in the mineral density of the femoral neck. These results suggest that bisphosphonates can be efficiently used together with exercise to reduce calcium loss and prevent some of the changes in mineral metabolism during long-term simulated microgravity.


Generation of mutant mice lacking surface expression of CD4 or CD8 gene targeting.

With the use of homologous recombination in embryonic stem cells, two new strains of mice lacking surface CD4 or CD8 expression have been generated. It is hoped that they will be useful mouse strains for the study of autoimmune diseases, tissue transplantation rejections and tumour rejections.


[Primary open angle glaucoma and low tension glaucoma--pathogenesis and mechanism of optic nerve damage].

The etiology, pathogenesis and mechanism of optic nerve damage in primary open angle glaucoma (POAG) and low tension glaucoma (LTG) were investigated by experimental glaucoma in monkey and by follow-up studies of many patients over 15 years, by pathohistological and immunohistochemical analysis. 1) LTG was proved to be a real glaucoma, showing pressure-dependent optic nerve damage. The pathological entity was a primary weakness of the lamina cribrosa (LC), and therefore even normal pressure could deform the LC. Due to backward distortion of LC the channels were disarranged and twisted, inducing mechanical optic nerve damage. There was no active vascular damage or vascular constriction at the site of the optic nerve damage. The filling defects of the advanced glaucomatous optic disc were not the cause of optic nerve damage, but the result of regressive vascular change after axon bundle loss. Splinter hemorrhage of the optic disc might be the result of the same process. 2) The weakness of LC might be induced by the abnormal metabolism of the extracellular matrix of the LC. 3) To arrest the progressive optic nerve damage in LTG, the intraocular pressure (IOP) should be maintained under 12, or ideally, 10 mmHg. 4) The optic nerve damage in POAG was not only pressure-dependent, but also dependent on the weakness of the LC, as in the case of LTG. In the early stage the IOP should be under 19 mmHg, in the advanced stage under 14 mmHg in order to arrest progression for over 15 years. 5) In advanced experimental glaucoma of monkeys, the LC showed reduction of elastin, fragmentation of collagen, and change of proteoglycans. 6) As in the LC, the trabecular meshwork also showed abnormal metabolism and abnormal deposits on the extracellular matrix in POAG, and LTG as well. 7) POAG and LTG might belong to the same family in which common abnormal metabolism of LC and trabecular meshwork induce various clinical features.


[Eye movement: experimental and clinical study using cine mode MRI].

As a special lecture at the 96th Annual Congress of the Japanese Ophthalmological Society in 1992, we presented experimental and clinical studies on eye movement using magnetic resonance imaging (MRI). MRI is more valuable than X-ray CT in defining external muscle anatomy in the orbit in a variety of pathological changes, and is free from the danger of radiation. Cine mode MRI, which was originally developed to observe cardiovascular function, was utilized experimentally for observation of eye movement. We invented two methods to produce a series of photographs. In the first method, "the moving eye method", the subjects were asked to perform 256 or 512 vertical and horizontal eye movements in synchronization with a sound trigger. In the second, "the fixed eye method", the subjects were asked to gaze at individual points in a 5 to 7 point sequence as indicated by the investigator. In both methods MRI data was generated and the resulting series of photographs were observed in cine mode on a television monitor. Displaying the MRI generated photographs in cine mode enables direct observation of the movement of the eye, optic nerve and extraocular muscles within the orbit. The moving eye method was more accurate in its portrayal of the actual movement of the eye, but the large number of eye movements, at least 256 movements, required about 5 minutes, and caused physical and mental fatigue for the subjects. The fixed eye method did not show actual movement of the eye, but was less fatiguing than the former method, and avoided several of its problems. A large number of ophthalmoplegia cases such as abducens palsy, oculomotor palsy, fracture of the orbital wall, foreign bodies in the orbit, Duane's syndrome, endocrine myopathy, esotropia, exotropia, etc., were examined using the fixed eye method of cine mode MRI. Using this technique, anatomical changes, such as atrophy or hypertrophy and the functional state demonstrated by the contraction and relaxation of the extraocular muscles could be investigated. Transposition of the extraocular muscles, an effective treatment for paralytic squint, was reexamined and a new surgical procedure was developed for abducens palsy. The measurement of the length, thickness and weight of the extraocular muscles from the MRI-generated photographs allowed for more accurate analysis. The three dimensional reconstructive method of MRI is very valuable for diagnosis in the orbit and is expected to contribute to future progress.


[Transurethral incision and fulguration of the bladder diverticulum: radicality and clinical efficacy].

We performed transurethral incision and fulguration of the bladder diverticulum (TUIFBD) for 8 diverticula in 6 patients. In combination with TUIFBD, one patient received transurethral resection of the prostate and another one transurethral lithotripsy of bladder stones. TUIFBD has been easily performed without any operative complications. All 8 diverticula had shrunken from one to two months after the operation but only one diverticulum had disappeared. Symptoms related to the bladder diverticulum had disappeared postoperatively in all cases. In conclusion, TUIFBD can be easily and safely performed in combination with other transurethral surgical procedures. TUIFBD may be insufficient for radicality, but is clinically effective.


[Clinical experience of urological surgery of the patients with hemostatic disorder or hemolytic disease].

This report deals with clinical experience of urologic surgery of patients with hemostatic disorder or hemolytic disease. In the past 5 years from May 1986, 14 operations were conducted in our clinic on 13 patients, consisting of 4 with von Willebrand disease (vWd), 1 with hemophilia B, 4 who had warfarin administration, 3 with essential thrombocythemia and 2 with spherocytosis. Almost all patients were treated hematologically before the urological operations. Except in 1 case, the post-operative course was favorable and under hematologic control. Massive bleeding in 1 case was obviously attributable to over-dosage of warfarin. It is difficult to determine the optimal dose of warfarin under an unstable hemostatic condition during the operation and recovery periods. However, it is possible to carry out urologic surgery for these patients under appropriate hematologic control, and ESWL was safely performed without medical treatment on 3 patients; 1 with vWd, 1 treated with warfarin and 1 with spherocytosis.


[Pheochromocytoma discovered in a pregnant woman: a case report].

A case of pheochromocytoma discovered at pregnancy is reported. The patient was a 27-year-old woman who had no symptoms before pregnancy. A sudden hypertensive attack occurred during vaginal examination at the 36th week of pregnancy. Magnetic resonance imaging (MRI) and ultrasonography showed a right adrenal mass. The level of catecholamine in blood and urine was beyond the normal limit. This patient was diagnosed as pheochromocytoma with pregnancy. Cesarean section was immediately done to avoid hypertensive crisis caused by spontaneous delivery. Blood pressure and blood volume were controlled by an alpha-blocker for one month after delivery, and, then the tumor was removed surgically. Pheochromocytoma with pregnancy is life-threatening for the mother and the fetus because of difficult diagnosis and complex clinical features. Early diagnosis and appropriate treatment are mandatory. Pathophysiological characteristics and the treatment of such specified statics are mainly discussed through our successful achievement.


[A case of neuroleptic malignant syndrome with acute renal failure].

Neuroleptic malignant syndrome is a potentially lethal side effect of neuroleptic drugs, characterized by fever, muscle rigidity, autonomic dysfunction, and altered consciousness. A 50-year-old female hospitalized three times in the past for psychiatric treatment was admitted to Umayabashi Hospital for treatment of a relapse of a schizophrenic psychosis. She had received 50 mg of chlorpromazine and one tablet of Vegetamin-A (chlorpromazine 25 mg, promethazine 12.5 mg, phenobarbital 40 mg). Approximately 24-36 hours later, the patient became febrile and lost consciousness, and eight days later, acute renal failure occurred with muscle rigidity. She was transported to Maebashi Red Cross Hospital to receive hemodialysis. On admission, the laboratory studies showed high levels of serum creatine phosphokinase, glutamic oxaloacetic transaminase, glutamic pyruvic transaminase, creatinine and blood urea nitrogen. She underwent hemodialysis for treatment of acute renal failure and recovered from it after 16 sessions of hemodialysis.


[A case of CA19-9 producing transitional cell carcinoma of the ureter effectively responsive to combination chemotherapy].

We report a case of CA19-9 producing transitional cell carcinoma of the right ureter effectively responsive to combination chemotherapy (methotrexate, vinblastine, doxorubicin and cisplatin (M-VAC) regimen) in a 53-year-old woman. The maximum level of serum CA19-9 showed 3,000 U/ml and clinical staging of the tumor was T4 N3 M0. Marked regression of the tumor was identified by computed tomographic scan and the level of serum CA19-9 returned to the normal range after 3 courses of M-VAC therapy. Right total nephro-ureterectomy and partial cystectomy was done and the surgical specimen revealed no viable tumors. She is alive without evidence of local recurrence or metastasis at 6 months after resection. The serum CA19-9 level was useful for monitoring the clinical course.


[Ureteral polyp: a difficult case to make a differential diagnosis with ureteral tumor].

We report a case of primary fibroepithelial polyp of the left ureter. The patient was a 34-year-old-man, complaining of left flank pain. An excretory urogram and retrograde pyelogram revealed left hydronephrosis and filling defect of the middle third of ureter. It was difficult to make a differential diagnosis with ureteral tumor. A frozen section revealed no malignancy and we performed partial ureterectomy and end-to-end anastomosis. We discussed the clinical features of adult primary ureteral polyp reported in the Japanese literature.


[Recurrent transitional cell carcinoma of the bladder in a young woman: report of a case].

A rare case of transitional cell carcinoma of the bladder in an 18-year-old female is presented. The chief complaint was gross hematuria and pain on urination. Transurethral resection was performed and pathological findings were low grade transitional cell carcinoma without invasion. During a 5-year follow up, she had relapse of the bladder tumor twice. Transitional cell carcinoma of the bladder in children and adolescents may be low grade, low stage and rarely recurrent, but the possibility of recurrence does exist. We emphasize the necessity of periodic cystoscopy for following up young adolescents with transitional cell carcinoma of the bladder.


[Pseudosarcomatous fibromyxoid tumor of the urinary bladder: a case report].

A 41-year-old man was referred to our clinic for gross hematuria. Cystoscopy revealed a 6 x 5 x 5 cm wide-based tumor located at the dome of the bladder. Pathological diagnosis of the biopsy was pseudosarcomatous fibromyxoid tumor. Microscopically this tumor was composed of spindle cells and myxoid stroma, and immunohistochemical and ultrastructural studies showed benign characteristics of this tumor. Therefore partial cystectomy was performed. It is important to recognize the histological characteristics of this essentially benign condition so that total cystectomy can be avoided.


[Prostatic cancer presenting as palpable lymph node metastasis--report of three cases].

Three cases of prostatic carcinoma with palpable metastatic lymph nodes are presented. In case 1, the intrapelvic lymph node metastases were recognized as an abdominal mass. In case 2 and 3, non-regional superficial lymph node metastases were palpable. Orchiectomy and anti-androgen therapy were effective in all cases.


[Giant epidermoid cyst of the scrotum: a case report].

A 74-year-old male with the chief complaint of painless enlargement of a mass in the scrotum was diagnosed as having a giant epidermoid cyst on July 8, 1991. He had no past history of injury or pain of the scrotum. Magnetic resonance imaging (MRI) of the scrotum demonstrated a well-circumscribed homogeneous mass, and was distinguished from both normal testes. Under the diagnosis of intrascrotal epidermoid cyst, the mass was resected surgically. The mass measured 23 x 15 x 15 cm, and it contained liquids. The pathological diagnosis was epidermoid cyst of the scrotum.


[Kallmann's syndrome in a child--a case report].

The patient was a male child 6 years and 6 months old. He visited our hospital because of bilateral cryptorchism and true phimosis. Since he was found to have fairly small testis, micropenis, and anosmia, endocrinological examination was performed. The plasma levels of luteinizing hormone (LH) and follicle stimulating hormone (FSH) were at the lower limit of normal values. LH gave a low reaction to the LH-releasing hormone test, while the reaction of FSH was near the lower limit of normal values. In the human chorionic gonadotropin test, there was no rise in the plasma levels of testosterone. Nor was there any reaction to the venous olfactory test with Alinamine (thiamine propyldisulfide). Accordingly, the patient was diagnosed as having Kallmann's syndrome. A search of the literature reveals few reports that deal with Kallmann's syndrome in infancy. Early diagnosis seems to be of significance, however, to institute early appropriate treatment to prompt the development of proper secondary sexual characteristics and ensure normal future fertility.


[Present status and controversy of treatment for renal cell carcinoma].

The current status and controversy of the treatment for renal cell carcinoma are reported. From 1980 to 1990, a total of 283 patients with renal cell carcinoma were treated in Nara Medical University and its affiliated hospitals. All patients were divided into two groups: M0 group (n = 217) and M1 group (n = 66). In addition, the M0 group patients were divided into two groups according to the followup study: M0-->M0 group (n = 194) and M0-->M1 group (n = 23). There was a significant difference between the survival of the M0 group and that of the M1 group (p < 0.001). A significant difference was also seen between the survival of M0-->M0 group and that of the M0-->M1 group (p < 0.001). The clinical and pathological factors which might be related to prognosis were analyzed. In the M1 group, high stage, high grade, non-surgical treatment for primary site and metastatic sites other than the lungs were found to be poor prognostic factors. In the M0-->M1 group, no prognostic factor was seen. These findings indicated that surgical treatment for the primary site in M1 patients should be performed. In addition, development of effective treatment for metastatic sites other than the lungs and effective postoperative adjuvant treatment would be necessary.


[Interferon therapy for advanced renal cell carcinoma].

To determine the effect of human lymphoblastoid interferon (HLBI) on metastatic renal cell carcinoma (MRCC), we performed two clinical trials. First, between 1982 and 1984, we performed a phase II study using 3 mega-units (MU) of HLBI daily in 25 eligible patients with MRCC. Six patients (24.0%) showed objective responses, including 2 with complete response (CR) and 4 with partial response (PR). Patients with a prior nephrectomy or with a good performance status were likely to respond to the therapy. Based on the above observation, we performed a prospective randomized trial to compare 2 different doses of HLBI following nephrectomy. Treatment consisted of HLBI, 3 MU intramuscularly 6 days a week in arm A and 1 MU intramuscularly 6 days a week in arm B. Treatments were started within 4 weeks after the nephrectomy and patients were evaluated every week for 1 month, and every month thereafter. Between 1985 and 1991, 16 patients were enrolled in arm A and 15 patients in arm B. Responses were seen in 5 (31.3%) of the 16 arm A patients (4 CRs and 1 PR) and 3 (20.0%) of the 15 arm B patients (1 CR and 2 PRs). Most responses occurred in patients with lung metastasis and favorable PS. There was no statistical difference in efficacy between the two arms. Hematologic toxicity was more frequent in arm A (43.8%) than arm B (13.3%). We conclude that further studies are needed to secure the clinical efficacy of HLBI for MRCC.


[Treatment of advanced renal cell carcinoma with interferon alpha and OK-432 (streptococcal preparation)].

A total of 12 patients with advanced renal cell carcinoma received interferon alpha (3 million units intramuscularly 6 times weekly) and OK-432 (5 KE (Klinische Einheit) intramuscularly twice weekly). Metastatic lesions appeared before operation in six patients and after operation in six patients. Among them 5 patients had received interferon therapy and this combination therapy was started after the judgment of progressive disease for interferon therapy. Eleven pulmonary and 5 bone metastases were evaluable. The median duration of the combination therapy was 89.3 weeks. There were 4 partial responses and no complete responses among the 12 patients, giving a response rate of 33.3%. The median duration of response was 25 months, with a range of 6 to 54 months. Responses were seen predominantly in patients in whom metastases appeared after operation (3 of 4 responders). However, regarding the individual organs, two complete and 2 partial responses were observed among 11 pulmonary metastases and 2 partial responses among 5 bone metastases. The survival period after discovery of the metastasis was 10 to 67 months and the 5-year survival rate was 70.5%. Almost all patients had fever and induration at the injection site. Other side effects included leukopenia, anorexia, and depression. This combination therapy is thought to be effective against bone or other organs metastasis resistant to interferon alone.


[Lymphokine-activated killer (LAK) therapy for metastatic renal cell carcinoma].

Fifteen patients with metastatic renal cell carcinoma (RCC) were treated by administration of autologous lymphokine-activated killer (LAK) cells given together with systemic administration of interleukin-2 (IL-2). Pulmonary metastases alone were found in 10 cases, pulmonary and mediastinal nodal metastases in 3, and pulmonary and bone metastases in 2. LAK cells, generated by incubation in 700 units/ml of IL-2 for 3-4 days, were intravenously administered once a week. In addition, beginning on the day of the first LAK cell infusion, 3.5 x 10(5) units of IL-2 were intravenously infused once or twice a day with occasional supplementation of 3.5 x 10(5) units of IL-2 on each day of LAK cell infusion. The total number of LAK cells and total amount of IL-2 administered per patient in this study ranged from 0.8 x 10(10) to 6.9 x 10(10) cells and from 10.2 x 10(6) to 74.9 x 10(6) units, respectively. As toxic effects caused by the infusion of LAK cells, headache, shaking chills, fever and leukocytosis were found in all cases. Side effects possibly induced by IL-2 infusion were tolerable fever, fluid retention (body weight gain of 2-3 kg) and eosinophilia. Out of 15 patients, a partial response was observed in 4 patients who had pulmonary metastases alone. One of the 4 patients with a partial response was clinically free of disease after undergoing a thoracotomy for resection of residual lesions, but a brain metastasis was detected 10 months after the thoracotomy. The remaining 3 patients are being closely followed up at present.(ABSTRACT TRUNCATED AT 250 WORDS)


[Lymphokine-activated killer (LAK) therapy for advanced renal cell carcinoma: clinical study on arterial LAK therapy and experimental study on LAK cell activity].

Experimental and clinical studies were conducted on lymphokine-activated killer (LAK) cell therapy for advanced renal cell carcinoma (RCC). The traffic assay using radiolabeled LAK cells indicated short-term but appreciable accumulation of LAK cells in the tumor site when trans-arterially infused. By contrast, systemically infused LAK cells were localized not to the tumor tissue but to the lung. Therefore, we began treatment of the patients with extrapulmonary metastases by means of regional arterial administration of LAK cells and those who had pulmonary metastases by a systemic LAK therapy. Regimen of Interleukin-2 (IL-2) administration was bolus infusion of 5 x 10 U IL-2 twice daily. Frequency of LAK cell administration varied from one to three times a week depending upon the patient's condition. Eight out of 16 metastases, such as bone, muscle, and lymph node metastases, in 9 patients treated by arterial LAK therapy showed regression. Side effects during LAK therapy were not serious. Past history of having chemotherapy was an unfavorable factor that could reduce the sensitivity to LAK therapy. Our laboratory study showed the production of Interferon (IFN)-gamma and Tumor Necrosis Factor (TNF)-alpha by LAK cells when preincubated with RCC cells, which may indicate the mechanism of LAK cell-mediated antitumor activity in vivo. The study also showed that LAK cells as well as monocytes preincubated with the supernatant of LAK cells damaged normal endothelial cells in vitro, which suggested the possibility that LAK therapy risks increasing the frequency of brain metastasis by damaging the blood-brain barrier.(ABSTRACT TRUNCATED AT 250 WORDS)


[Circumvention of the intrinsic multidrug-resistance in renal cell carcinoma].

Most of renal cell carcinomas (RCCs) are refractory at the start of chemotherapy. We have demonstrated that the frequently elevated expression of the multidrug resistance gene (MDR) in RCCs is associated with the intrinsic vinca alkaloids and anthracyclines resistance. The preliminary clinical trials using verapamil or amiodarone in combination with vinblastine or doxorubicin to overcome multidrug-resistant (MDR) tumors could not achieve satisfactory results owing to severe cardiovascular toxicities of such reversing agents. In the present study, we studied the sensitizing ability of bis-benzyl-isoquinoline (cepharanthine) and SDB-ethylenediamine (N-1379) in natural MDR kidney cancer cells. Cepharanthine remarkably sensitized vinblastine and doxorubicin sensitivities in those cells with high MDR RNA levels. From a clinical point of view, cepharanthine seems to be a potent and less toxic agent to treat natural MDR kidney cancers.


[Renal cancer specific antitumor activities of a mouse monoclonal antibody K2.7 to human renal cell carcinoma].

We have prepared a mouse monoclonal antibody (mAb) K2.7 (IgG3) by immunizing mice with renal cancer cell (RCC) line OS-RC-2. In a serological analysis by protein A assay, 25 out of 31 RCC lines reacted with the mAb K2.7 but none of the 50 other cell lines from different organs except for 2 cell lines did. In immunohistological analysis by indirect immunoperoxidase assay, 66 out of 72 renal cancer tissues showed positive staining. Metastatic lesions of renal cancers also reacted similarly to the primary lesion. Some restricted normal tissues including tubules of normal kidney showed positive staining. Specific antitumor activities of mAb K2.7 against RCC lines were investigated in vitro by complement dependent cytotoxicity (CDC) and antibody dependent cell mediated cytotoxicity (ADCC) assays. In CDC assay, all of the 9 RCC lines were killed by mAb K2.7 and normal human serum, and killing activities of mAb K2.7 presumably depend on the number of antibody molecules bound to the cell surface. Sera from 9 patients with renal cancers including low and high stages showed the same killing activities to 3 RCC lines as normal human serum. In the ADCC assay, peripheral leukocytes (PBLs) from 4 healthy donors showed strong killing activities to RCC lines. Killing activity differed with the individual. PBLs from the same 9 patients as in the CDC assay showed significantly positive killing activity against 3 RCC lines. These findings suggest the usefulness of mAb K2.7 for the specific immunotherapy of renal cancer.


[Anti-interleukin-6 (IL-6) therapy of IL-6-producing renal cell carcinoma].

Interleukin-6 (IL-6) has been demonstrated to be an autocrine growth factor of renal cell carcinoma in vitro and released IL-6 has been thought to elicit the acute phase response in vivo. We investigated the possibility of anti-IL-6 therapy of IL-6-producing renal cell carcinoma. There was a dose-dependent decrease in the number of colonies formed in vitro of NC65 renal cell carcinoma cell line in the presence of dexamethasone which is known to inhibit the induction of IL-6 messenger RNA. IL-6 receptor antisense oligonucleotide and anti-IL-6 receptor antibody also showed growth inhibition of NC65 cells. IL-6 antisense oligonucleotide and anti-IL-6 antibody did not alter the proliferation of NC65 cells. These findings suggest that inhibitors of IL-6 production or IL-6 function may be useful for some renal call carcinoma patients.


[Clinical evaluation of usefulness of cefixime (200 mg administered once daily) in the treatment of acute uncomplicated cystitis].

A comparative study of cefixime (CFIX), a new oral cephem antibiotic, was carried out at the Department of Urology, Nagoya University Hospital and its four affiliated hospitals to evaluate the clinical efficacy and safety of two dosage regimens of CFIX, given either in twice daily doses (BID group) or once daily dose (UID group), in the treatment of acute uncomplicated cystitis. Forty six female patients (BID group) were administered the daily dose of 200 mg in two divided doses for 3 days, 30 female patients (UID group) were administered 200 mg once daily for 3 days. The clinical efficacy was evaluated in 33 cases from the BID group and in 22 cases from the UID group, respectively, according to the criteria recommended by the Japan UTI Committee. In the BID group, the clinical efficacy was evaluated as excellent in 18 cases, moderate in 13 and poor in 2, with an overall clinical effectiveness rate of 94%. In the UID group, it was evaluated as excellent in 9 cases, moderate in 12 and poor in 1, with an overall clinical effectiveness rate of 96%. Safety was monitored in 71 patients, and only one case of stomatitis was seen in the UID group. This findings suggest that 200 mg once daily dosing regimen of cefixime is as effective as 100 mg twice daily dosing regimen in treatment of acute uncomplicated cystitis, and is well tolerated in terms of safety.


A new method of administration of topical nasal extracts. Immunoaerosol therapy.

Topical nasal immunotherapy (TNI) is a therapeutic option in residual rhinitis. Adverse reactions are common with pollen extracts and often are related to the phenol and thimerosal conservatives. This study sought to determine the clinical effectiveness of two methods of administration of TNI. Twenty-eight patients with allergic perennial rhinitis treated for 2 years with parenteral semidepot immunotherapy were divided into two groups of 14 patients: group A receiving conventional aerosol nebulization (TNE), and group B, which received TNAI using a type F aerosol electrocompressor. Clinical response and tolerance to TNI were evaluated using scores for signs and symptoms. The conclusions were: Both group A and group B exhibited statistically significant differences between baseline and post-immunotherapy parameters (p < 0.001). There were no statistically significant differences in the degree of improvement achieved in the two groups. The main advantages of TNAI were better tolerance of the D. pteronyssinus extracts, perhaps due to the elimination of conservatives, and the guarantee of correct administration of the dose and control of minimum reactions. For these reasons it is a viable therapeutic option in allergic perennial rhinitis previously treated for two years with parenteral semidepot immunotherapy.


Expression of the epidermal growth factor receptor in squamous carcinoma cell lines of the larynx and hypopharynx.

Characterization of the EGF-R has been carried out on five squamous carcinoma cell lines of the head and neck region (FaDu, HLaC-78, HLaC-79, UM-SCC-17A and 17-B). The results have been compared with those from a spontaneously immortalized aneuploid human keratinocyte cell line (HaCaT) and cultured fresh skin keratinocytes. A monoclonal antibody directed against the external region of the EGF-R was used for APAAP-immunostaining and flow cytometric analysis. We observed an important heterogeneity in the EGF-R expression of the different cell lines. The highest overexpression of the EGF-R was found on the cell line UM-SSC-17A. The results of our flow cytometric studies confirm and extend previous studies in which either radioimmunoassay of tissue extracts or immunocytochemistry of tissue sections showed an altered expression in head and neck squamous carcinoma. The cell line UM-SSC-17A seems to be most useful in elucidating the role of the EGF-R expression in the behaviour of head and neck epidermoid malignancies.


Complement system in malnutrition.

The total complement and C3 and C4 components serum levels were assessed in vitro in forty children suffering from severe and moderate protein-calorie malnutrition in the 2 to 5 year age group. Twenty well-nourished children of the same age were as a control group. The results in the three group showed no significant differences.


Cellular immunity in paracoccidioidomycosis.

Paracoccidioidomycosis was studied in 62 patients from Brazil in the 10 year period between 1978 and 1988. In 46 patients included in a first group, the disease was active and in 16 patients included in a second group, the disease was cured. The study was conducted according to both the clinical form of the disease and the response to paracoccidioidin in both groups. In the first group, 10 patients presented the acute form, 12 presented the chronic unifocal form and 24 had the chronic multifocal form of the disease. As to the response to paracoccidioidin, in the first group 16 patients were negative and 30 were positive; in the second group, 11 were positive and 5 were negative. An immunological study was performed in all patients using in vivo methods such as skin tests and sensitization to DNCB and in vitro techniques such as total lymphocyte counts, T and B cell counts, leukocyte migration inhibition test, chemotaxis of total leukocytes and mononuclear leukocyte phagocytosis.


Study of the possible crossed reactivity between D. pteronyssinus and non pyroglyphide acarus. 1. Skin tests and FAST inhibition.

On 132 patients with case history of rhinitis and/or asthma in a domestic environment and with positive cutaneous tests contrasted with D. pteronyssinus, we have made cutaneous tests compared to said antigen and compared with D. farinae, L. destructor and A. siro, with extracts 5000 E/ml (Noon Units), as well as FAST inhibition, using D. pteronyssinus in its solid phase and all the above mentioned extracts in their liquid phase. Our results show that the frequency of D. pteronyssinus positivities in prick is greater than the other mites as well as the intensity of the response expressed in the size of the wheal showing significant differences between those found for D. pteronyssinus and those obtained with other mites. In turn those obtained with the D. farinae are significantly greater than those obtained with non-pyroglyphide mites. In FAST inhibition we only found a good correlation for D. pteronyssinus-D. pteronyssinus and D. pteronyssinus-D. farinae and there is no good correlation between the other mites. The correlation coefficients differ significantly except for those of the pyroglyphides, and the regression equations show a lack of parallelism in the regression lines. Consequently, on the basis of this study, we conclude that there is no crossed reactivity between D. peteronyssinus and non-pyroglyphide mites.


Refractory thrombocytopenia. A myelodysplastic syndrome that may mimic immune thrombocytopenic purpura.

The French-American-British classification scheme of myelodysplastic syndromes includes a category of refractory cytopenia that includes refractory thrombocytopenia (RTC). Because dysmegakaryopoiesis manifesting as an isolated cytopenia can be difficult to identify morphologically and because it may be accompanied by megakaryocytic hyperplasia, RTC may be confused with idiopathic thrombocytopenic purpura. A review of 1,220 cases of myelodysplastic syndromes at Mayo Clinic Jacksonville and Mayo Clinic Rochester from 1979 to 1990 yielded 9 cases (0.7%) of isolated thrombocytopenia (RTC) associated with clonal chromosome abnormalities. Review of 319 marrow chromosome analyses performed at the cytogenetics laboratory at Mayo Clinic Rochester from 1979 to 1990 for patients with low platelet count yielded two additional cases of RTC (0.6%). Of the 11 RTC cases, 3 previously had been misdiagnosed as idiopathic thrombocytopenic purpura. All patients had oval macrocytes in peripheral blood smears and abnormal megakaryocyte morphology in bone marrow aspirates, lacked antiplatelet antibodies, and did not have splenomegaly on clinical examination. The most common clonal chromosome abnormalities involved chromosomes 3, 5, 8, or 20. Steroid therapy was ineffective. Clinical and laboratory findings can establish the diagnosis of RTC and allow the physician to avoid recommending inappropriate therapy (steroids or splenectomy) for these patients.


Serum ferritin measurement and the degree of agreement using four techniques.

Four commercial assay kits to measure serum ferritin were compared to establish the degree of agreement and interchangeability between the different techniques based on the intraclass correlation coefficient (ri). Radioimmunoassay, microparticle enzyme immunoassay, enzyme-linked immunosorbent assay, and chemiluminescent immunoassay systems were used. The Pearson product-moment correlation factor (r) between any two methods was at least 0.98, and the intercept of the regression equations ranged from -0.613 to 3.797, indicating that the methods were comparable. Furthermore, the intraclass correlation coefficient (ri) was at least 0.98, suggesting that the methods were interchangeable.


Congenital dyserythropoietic anemia type II diagnosed in a 69-year-old patient with iron overload.

Congenital dyserythropoietic anemia type II is a rare disorder that is often diagnosed in patients before age 20 years. Patients with this disorder, which is also called hereditary erythroblastic multinuclearity associated with a positive acidified serum lysis test, may have symptoms of iron overload. The purpose of this case report is to alert physicians to consider the diagnosis of congenital dyserythropoietic anemia type II in elderly patients who have anemia and iron overload.


A rapid method to isolate platelets from human blood by density gradient centrifugation.

Platelets can be damaged easily or activated during isolation, making them unsuitable for functional studies. The most common technique for isolating platelets involves centrifugation. Although gentler methods have been devised to isolate platelets by density gradient centrifugation or electrophoresis, these techniques either result in a relatively dilute platelet preparation or are time-consuming. A simple, gentle technique for isolating concentrated platelet preparations for experimental or clinical use is reported. Freshly drawn whole blood was spun over a commercially available density gradient medium for 30 minutes. The mononuclear cell layer (which also contains most of the platelets) was collected and nucleated cells were pelleted by centrifugation. The recovery of platelets was about 60%. Contamination with leukocytes was less than 1%, and the platelet concentration was about 130% of blood concentration. Higher concentrations can be obtained if more whole blood is layered onto the Mono-Poly Resolving Medium (MPRM; Flow Laboratories, McLean, VA). About 10% of the platelets expressed the activation marker GMP-140 by flow cytometric analysis. They could be activated by thrombin so that 70% to 90% of the platelets expressed GMP-140. Thus, this technique can rapidly and easily yield a functionally intact platelet preparation. This preparation can be purified again if needed. No specialized skills or equipment are needed. A significant advantage of the method is that platelets can be obtained from thrombocytopenic patients in final concentrations that are high enough to use for platelet function testing.


Excessive fibrinolysis in amyloidosis associated with elevated plasma single-chain urokinase.

Severe bleeding resulting from excessive fibrinolysis has been observed in patients with primary amyloidosis. The authors studied a patient with this hemostatic disorder before and during therapy with epsilon-aminocaproic acid. Excessive fibrinolysis was associated with depressed plasma concentrations of coagulation Factors XII, XI, high-molecular-weight kininogen, and Factors VIII and V; and plasminogen and alpha-2-plasmin inhibitor. These deficiencies were corrected with treatment. The functional and antigenic concentrations of tissue plasminogen activator and plasminogen activator inhibitor in the patient's plasma were normal. Urokinase-type activator activity and antigen were three to five times elevated in the patient's plasma. Results of immunoprecipitation showed that single-chain urokinase-type activator was the primary urokinase-type activator species in the patient's plasma. Excessive fibrinolysis in patients with amyloidosis results from increased plasma single-chain urokinase-type activator activity.


Development of alloanti-Jka in a patient with hemolytic anemia due to autoanti-Jkb.

Autoanti-Jkb and a transient autoanti-E were identified in a patient with autoimmune hemolytic anemia, and red blood cells negative for Jkb and E antigens were transfused. Twelve weeks after transfusion, the autoantibody appeared to have developed broad specificity. However, autoadsorption studies revealed that the broad reactivity was due to the development of alloanti-Jka in addition to the autoanti-Jkb. Distinguishing this combination of alloanti-Jka plus autoanti-Jkb from an autoantibody with broad specificity will be important in selecting Jka antigen-negative red cells for subsequent transfusions. This case emphasizes the importance of additional serologic testing to detect alloantibodies in patients with broadly reactive warm autoantibodies.


Parental and family predictors of behavior problems in inner-city black children.

Studied contributions of maternal psychological distress, family stress load, maternal and family risk factors, and family coping strategies in predicting behavior problems in 441 inner-city black primary-grade children. Results indicated maternal psychological distress and high family stress load were associated with high child behavior problems. Family coping strategies offered no protection against risk, while coping with life difficulties by reframing them was detrimental to child behavioral adjustment. Active help-seeking strategies (i.e., family mobilization, acquiring social supports) served to moderate the effects of maternal psychological distress and family risk attributes for boys, but exacerbated the effects of dysfunctional maternal social and psychiatric histories for girls. Implications for understanding vulnerability and resilience in inner-city black children and recommendations for future research are discussed.


How did it work? An examination of the mechanisms through which an intervention for the unemployed promoted job-search behavior.

Conducted process analysis of treatment mediation effects (Judd & Kenney, 1981) on longitudinal data from a large randomized field experiment with 928 recently unemployed persons. The experimental treatment included an intervention that succeeded in promoting quality reemployment outcomes, as described in earlier reports (Caplan et al., 1989; Vinokur et al., 1991). Using Ajzen's theory of planned behavior (Ajzen, 1985, 1988), the analyses examined the mediating effects of job-search self-efficacy, attitude, norms, and intention on job-search behavior. The results provided substantial support for the theory of planned behavior and demonstrated the mediational role of job-search self-efficacy. For both 1- and 4-month posttests, job-search self-efficacy was shown to mediate the effects of the intervention through its direct effects on job-search intention and on short term job-search behavior, as well as through its indirect effects on subjective norms and attitude. However, in the longer term 4-month posttest, exposure to the intervention had a direct effect on job-search behavior. This long-term direct effect of the intervention was hypothesized to reflect the influence of inoculation against setbacks which is essential for sustaining the long-term behavioral efforts involved in job seeking.


Prediction of early social and academic adjustment of children from the inner city.

Investigated predictors of five measures of early school adjustment for an ethnically diverse cohort of 683 inner-city kindergartners and first graders. Data from 2 consecutive years were collected from teachers, school records, and children. A multiple-regression preduction model significantly explained children's competence behavior, problem behavior, reading achievement, mathematics achievement, and school absences. Prior adjustment and sociodemographic factors explained a majority of the variance in adjustment. Perceived quality of parent involvement was signifcantly related (in the expected direction) to all five outcomes. Exposure to life events was significantly associated in the expected direction with competence behavior, problem behavior, and school absences but not with reading and mathematics achievement. Together, parent involvement and life-event variables explained as much as 12% of the variance in adjustment independent of sociodemographic and prior adjustment factors. The role of family and school factors in the adjustment of children at risk is discussed [corrected].


A longitudinal study of the effects of various crime prevention strategies on criminal victimization, fear of crime, and psychological distress.

Examined the effects of precautionary behavior on subsequent criminal victimization, fear of crime, and psychological distress. A sample of 538 adults was interviewed three times at 6-month intervals. Four different aspects of precaution were assessed: vigilance (alertness), locks (access control), neighbors (informal cooperation), and professionals (formal programs). In logistic regressions that controlled for 14 risk factors, precaution had no preventive effects on the occurrence of subsequent crimes. LISREL models revealed that use of neighbors was the only precaution not to increase fear of crime, although both locks and neighbors showed a capacity to buffer the effects of fear on generalized distress. It was concluded that the most promising strategy was protective neighboring. Altogether, however, the promotion of citizen-initiated prevention appears highly inadequate as a policy response to problems of crime and fear.


Bereavement support groups: who joins; who does not; and why.

Compared widowed spouses who joined (n = 40) bereavement support groups (BSGs) during the first 13 months of bereavement with those who declined to join (n = 96). Controlling for gender, age, and socioeconomic status, no differences were found for perceived levels of social support, but joiners, compared with nonjoiners, reported experiencing more stressful events and scored significantly higher on measures of depression, anger, anxiety, and subjective stress. Nonjoiners and, to a lesser extent, joiners viewed those attending groups as less self-sufficient (e.g., need help, lonely), suggesting a mildly stigmatizing image of BSGs. A dialectical model is proposed in which BSG utilization rates are seen as the product of an avoidance-avoidance conflict involving the choice between suffering emotional distress on one's own or the perceived stigma of joining a BSG. Implications for future research on participation in self-help and mutual support groups are discussed.


Family characteristics of children who self-select into a prevention program for children of alcoholics.

Evaluated the efficacy of a self-selection recruitment process designed to attract fourth-, fifth-, and sixth-grade children into a school-based prevention program for children of alcoholics. Participants were 296 families comprising one child and either one or both parents. Family members' self- and collateral reports were used to assess parental problem drinking, family characteristics, and individual pathology. Analyses revealed that the recruitment process was not effective in recruiting children of alcohol-abusing parents. Furthermore, families in which children received parental consent to participate in the prevention program were indistinguishable from families whose children either showed interest without obtaining consent or showed no interest at all. Implications for recruitment strategies for future prevention programs for children of alcoholics are discussed.


Relationship of squamosal suture to asterion in pongids (Pan): relevance to early hominid brain evolution.

Based on 244 measurements of the relationship of the squamosal suture to the landmark asterion in 49 chimpanzee skulls, it is shown that in the normal lateral view the squamosal suture is very rarely inferior to asterion. In hominid crania, the squamosal suture is always well superior to asterion. Even in Pan, that part of the squamosal suture most homologous with the remnant found on the Hadar AL 162-28 Australopithecus afarensis hominid cranial fragment is very rarely inferior to asterion. Such variability suggests that Falk's (Nature 313:45-47, 1985) orientation of the Hadar specimen is incorrect; she places asterion superior to the position of the squamosal suture if projected endocranially. The implication for the brain endocast is that, however the fragment is oriented, the posterior aspect of the intraparietal (IP) sulcus is in a very posterior position relative to any chimpanzee brain. The distance from the posterior aspect of IP to occipital pole is twice as great in chimpanzee brain casts than on the Hadar AL 162-28 endocast, even though the chimpanzee brain casts are smaller in overall size. This suggests that brain reorganization, at least as exemplified as a reduction in primary visual striate cortex (area 17 of Brodmann), occurred early in hominid evolution, prior to any major brain expansion.


Evolution of the power ("squeeze") grip and its morphological correlates in hominids.

The "squeeze" form of power grip is investigated for the purposes of clarifying the hand posture and activities associated with the grip, assessing the potential in chimpanzees for using the grip, and identifying morphological correlates of an effective power grip that may be recognized in fossil hominid species. Our approaches include: (1) the analysis of the human grip, focusing on both the hand posture involved and hand movements associated with use of the grip in hammering; (2) the analysis of similar chimpanzee grips and associated movements; (3) comparative functional analysis of regions in the hand exploited and stressed by the grip and its associated movements in humans; and (4) a review of the literature on the power grip and its morphological correlates. Results of the study indicate that humans use a squeeze form of power grip effectively to wield cylindrical tools forcefully as extensions of the forearm. Several morphological features occur in high frequency among humans which facilitate the grip and are consistent with the large internal and external forces associated with it in hammering and in other tool-using activities. Chimpanzee hand postures resembling this form of human power grip are not fully comparable and lack some of these morphological correlates that facilitate its use. The hand of Australopithecus afarensis does not appear to have been stressed by use of the grip, but there is some evidence for this type of stress in the metacarpals from Sterkfontein Member 4. Hands from Olduvai and Swartkrans do not provide sufficient evidence for assessment of power grip capabilities.


Meningeal arteries in rhesus macaques (Macaca mulatta): implications for vascular evolution in anthropoids.

The branching patterns of meningeal arteries are reported for 200 endocast hemispheres representing rhesus monkeys (Macaca mulatta) of known cranial capacity. We detect five basic patterns for the branching of the anterior division of the middle meningeal artery and its relationship with the anterior meningeal artery. These results confirm and elaborate trends published for much smaller samples that were based on direct dissections of rhesus monkey arterial patterns. The most common pattern is that in which the anterior meningeal artery dominates the blood supply above the rostral part of the middle cranial fossa. Analysis of cranial capacities reveals that presence of this pattern on both sides of endocasts is associated with increased cranial capacity. When studied in light of published reports of anatomical dissections of cranial arteries in apes and human embryological data, the anterior meningeal artery in rhesus monkeys appears to be a possible homologue of the lacrimal meningeal artery in apes and the anterior branch of the middle meningeal artery in humans. This finding provides a step towards understanding cranial vasculature homologies that may be useful for accurately scoring the branching patterns of the meningeal arteries in monkeys, apes, and humans.


Medieval example of metastatic carcinoma: a dry bone, radiological, and SEM study.

An elderly male skeleton from medieval Canterbury displayed evidence of DISH and metastatic carcinoma. The dry bone findings, SEM, and radiography suggest a primary focus in the prostate. A review of the palaeopathological literature has shown that such a finding is extremely rare in archaeological remains. This is the first reported case of prostatic carcinoma from medieval England.


Paleohistology of Paget's disease in two medieval skeletons.

Paget's disease has been ascribed several times to specimens of archeological bone but, in the absence of microscopic examination, the evidence remains insubstantial. Suspected metabolic bone disease is described here in the archeological remains of a skeleton from a 16th century burial ground at Wells Cathedral, England and from a single medieval sacrum recovered from a large deposit of disarticulated bones from a churchyard at Barton-on-Humber, England. Radiographs showed apparent structural abnormality in one femoral shaft and calcaneus and in the isolated sacrum. Histomorphometry on undecalcified bone cores confirmed the regions of abnormality and showed not only increased trabecular width but also areas of "mosaic" woven bone together with extensive resorption cavities; these features contrasted with the normal structure and organized lamellar bone from sites elsewhere. Despite post-interment changes in surrounding tissues, the morphological stability of some of the osteocytes was remarkable. Preservation of the histology was sufficient to permit the assignment of a metabolic bone disorder and the nature of the sclerosis was consistent with Paget's disease.


Estimating femur and tibia length from fragmentary bones: an evaluation of Steele's (1970) method using a prehistoric European sample.

Steele's (1970) regression method for estimating femur and tibia length from fragmentary bones is tested on a sample of complete femora (female N = 26; male N = 33) and tibiae (female N = 16; male N = 22) from a number of European Mesolithic and Neolithic sites. Over half of the regression equations given by Steele for predicting maximum length of the bone from the length(s) of one or more of its constituent segments are shown to produce inaccurate predictions in this test sample. However, a closer evaluation of these results, including calculation of regression equations for the test sample itself, reveals that this inaccuracy does not derive from any inherent flaw in Steele's method. Rather, it is shown that differential distribution of maximum bone length among the various bone segments as defined by Steele may occur due to variation in muscular activity pattern and intensity. This argues for the retention of Steele's basic method, with care being taken to match closely the activity pattern typical of the sample from which regression equations are derived with that of the population to which the equations are to be applied. The equations calculated in this study thus are provided for use where deemed appropriate.


Measurement of subcutaneous adipose tissue using ultrasound images.

The objectives of this paper are to explore the potential of the ultrasound technique to quantify subcutaneous adipose tissue, and to explain the differences between skinfolds and ultrasound measurements across a large range of ages and levels of adiposity. The sample consisted of 115 men and 117 women aged 35 to 51 years, 132 girls and 145 boys aged 12 to 20 years. Subcutaneous fat thickness was measured at four sites using skinfolds calipers, and at seven sites using a real-time B-mode ultrasound scanner. Anthropometric measurements were obtained, and percent body fat was estimated using electric impedance. The agreement between skinfolds and ultrasound measurements was calculated for each age and sex group. The agreement between techniques, and the levels of correlation between body composition and fatness measurements were high in the sample of young men. However, the results were less consistent in the other groups. Site specific differences were also noted.


Falsification of a single species hypothesis using the coefficient of variation: a simulation approach.

Dental variation remains an important criterion for assessing whether a morphologically homogeneous fossil primate sample includes more than one species. The Coefficient of Variation (CV) has commonly been used to compare variation in a fossil sample of unknown taxonomic composition with that of extant single-species samples, in order to determine whether more than one species might be present. However, statistical tests for differences between fossil and single species reference sample CVs often lack power, because fossil samples are usually small and confidence limits of the CV are consequently large. The present study presents a new methodology for using the CV to test the hypothesis that a sample represents only one species. Simulated sampling distributions of single-species and pooled-species CVs are generated based on variation observed in dental samples of extant Cercopithecus species. These simulated distributions are used to test a single-species hypothesis for 13 different combinations of two or three sympatric Cercopithecus species across four dental characteristics at different sample sizes. Two different ways to generate the reference value of the CV are used. Results show the proposed methodology has substantially greater power than previous methods for detecting multiple-species composition, while maintaining an acceptable Type I error rate. Results are also presented concerning the dependence of power on sample size and on the average difference between means in a pooled-species combination.


Probit and survival analysis of tooth emergence ages in a mixed-longitudinal sample of chimpanzees (Pan troglodytes).

Tooth emergence data from a mixed-longitudinal sample of 58 chimpanzees of known age were analyzed using probit and survival techniques to produce median emergence ages, ranges of variability, and emergence sequences for primary and permanent teeth. Between-group comparisons were made to test for statistically significant differences in emergence ages. No such differences were found between right and left sides, or between maxilla and mandible, for any primary or permanent teeth. Male-female comparisons did demonstrate significant emergence-age differences for some teeth, although they were not always bilaterally symmetrical. More complete data are required to further clarify the nature of sex differences in tooth emergence in chimpanzees. Regression models for age prediction from the number of emerged teeth were generated and indicate that males achieve a given number of emerged teeth at a significantly later age than females. However, when fewer than five teeth have emerged, males are predicted to be younger than females. The sizable root mean square error values for these models suggest that this method of age prediction has limited usefulness owing to the amount of variability in timing of tooth emergence in chimpanzees. The implications of these data for studies on tooth emergence in early hominids are addressed.


Parietaria pollinosis: a review.

Species of the genus Parietaria (pellitory) are a prevalent cause of allergy in the Mediterranean area and the most important in some European regions such as southern Italy and coastal Spain (14, 26, 27, 29, 30, 31, 36, 59, 69). Up to now, however, Parietaria has received little attention in northern Europe and the US because of its limited regional distribution. Therefore, less is known about Parietaria allergy than about other inhalant allergens such as those of grasses, ragweed, and mites. During the last 5 years, only 31 reports on Parietaria allergy have appeared in the literature, as compared with 37 papers on birch pollen. This ratio may appear unbalanced, considering that millions of people suffer from pollinosis caused by Parietaria, while a much smaller number have rhinitis and/or asthma caused by birch pollen. The increasing movement of people throughout Europe and to and from the US is reason to broaden our knowledge of patterns of inhalant allergy in each geographic area, especially where tourism and immigration are high. This paper briefly reviews available data and personal studies on the botanical, aerobiological, immunochemical, and clinical features of Parietaria allergy.


Human Th1 and Th2 lymphocytes: their role in the pathophysiology of atopy.

In human beings, as in mice, two distinct patterns of cytokine secretion have been defined among CD4+ helper T-cell clones. Human type 1 helper (Th1), but not type 2 helper (Th2), cells produce interleukin-2 (IL-2), gamma-interferon (IFN-gamma), and tumor necrosis factor-beta, whereas Th2, but not Th1, cells secrete IL-4 and IL-5, but not IL-2 or IFN-gamma. Other cytokines, such as IL-3, IL-6, GM-CSF, or TNF-alpha, are produced by both Th1 and Th2 cells. Th0 cells, a third Th subset, show combined production of Th1- and Th2-type cytokines. The different cytokine patterns are associated with different functions. In general, Th2 cells provide an excellent helper function for B-cell antibody production, particularly of the IgE class. On the other hand, Th1 cells are responsible for delayed type hypersensitivity reactions and are cytolytic for autologous antigen-presenting cells, including B cells. Most allergen- or helminth-antigen-specific human CD4+ T-cell clones exhibit a Th2 phenotype, whereas most clones specific for bacterial antigens show a Th1 profile. Allergen-specific Th2 cells seem to play a crucial role in atopy. These cells induce IgE production via IL-4 and favor the proliferation, differentiation, and activation of eosinophils via IL-5. In addition, Th2-derived IL-3 and IL-4 are mast-cell growth factors that act in synergy, at least in vitro. Recent evidence indicates that allergen-specific Th2 cells are selectively enriched in tissues affected by allergic inflammation, such as the bronchial mucosa of subjects with allergic asthma.(ABSTRACT TRUNCATED AT 250 WORDS)


Heterozygous alpha 1-antichymotrypsin deficiency may be associated with cold urticaria.

Proteins of the serpin family (serine protease inhibitor) control key steps in the inflammatory, coagulation and complement systems. C1-inhibitor deficiency predisposes to hereditary angioneurotic oedema, and other serpins control proteolytic enzymes that may cause complement activation or the forming of oedema. We investigated whether deficiency of proteins of the serpin family may predispose to cold urticaria and therefore screened 7 male patients with severe cold urticaria for the presence of deficiency alleles of some of the members of the serpin antiprotease family. There were no findings of C1-inhibitor, alpha 1-antitrypsin, alpha 2-antiplasmin, antithrombin III, tissue plasminogen activator inhibitor or thyroxine binding protein deficiency. The prevalence of heterozygous alpha 1-antichymotrypsin deficiency was significantly higher than expected (prevalence ratio 25.8 (95% confidence interval 6.0-112), p < 0.0001). This finding is in concert with previous studies that have shown lower mean levels of alpha 1-antichymotrypsin among patients with cold urticaria and suggests that heterozygous deficiency of this antiprotease, which controls neutrophil cathepsin G and mast cell chymase may predispose to cold urticaria. The present series is, however, small and the results need confirmation in larger materials.


Clinical evaluation of CAP System and RAST in the measurement of specific IgE.

We investigated the diagnostic value of a new in vitro test, Pharmacia CAP System (Pharmacia Diagnostics AB, Uppsala, Sweden), for the quantitative measurement of allergen-specific IgE antibodies by comparison with RAST in 2 groups of patients, 71 atopic and 48 non-atopic. In the last 20 years RAST has supplied a good diagnostic tool, but this test presents some problems, the main one being sensitivity. The new test has a solid phase able to bind even very small amounts of specific IgE and an anti-IgE tracer with very low cross-reactivity with other immunoglobulins, thus presenting more favourable conditions. From the analysis of our results, Pharmacia CAP System gave higher sensitivity (94% compared to 88% of RAST) with no loss of specificity (96% for both tests). The reliability of these results is ensured by the proper selection of patients who were all suffering from pollinosis and were clinically diagnosed as certainly hypersensitive to a single pollen. A positive trend was found between severity of asthma and levels of specific IgE for timothy. Pharmacia CAP System appears to identify a larger number of atopic patients than RAST.


Evidence of a common regulation of IgE and IgG-subclass antibodies in humans during immunotherapy.

Based on a 3-year prospective study of 20 pollen-allergic patients, where a detailed analysis of the IgE, IgG1 and IgG4 immune response was performed, we propose that a common regulatory mechanism exists between the IgE and IgG1 synthesis and between IgE and IgG4 synthesis during immunotherapy. It was found that the IgE immune response to a number of antigens was quantitatively diminished during the period of immunotherapy when IgG1 was present early (week 12), and for other antigens there was a rise in IgE without an early IgG1 antibody response. Additionally, it was found that for some antigens a rise in IgE antibodies was contrasted by a fall in the IgG4 antibody response and for other antigens the opposite was true, indicating a regulatory mechanism between the IgE and the IgG4 synthesis. A statistical analysis showed that these findings were statistically significant at the 0.01% level for the IgE/IgG1 relationship and at the 0.05% level for the IgE/IgG4 relationship. These findings could have implications for future immunotherapy regimens.


Distribution of serum IgE in children and adolescents aged 7 to 16 years in Copenhagen, in relation to factors of importance.

The distribution of total serum-IgE and factors of importance for the level of IgE was studied in a random sample of 508 children and adolescents, aged 7-16 years, from Copenhagen. A detailed history about asthma, rhinitis, dermatitis and urticaria was obtained, and a physical examination, skin prick test with 9 common allergens, lung function test, bronchial challenge with inhaled histamine and exercise, and measurement of IgE (kU/l) were performed. The distribution of IgE among children and adolescents was found to exhibit a log normal distribution and a positive skin prick test, allergic symptoms, a family history of allergic diseases, age and smoking were found to be significantly related to an increased level of IgE. No relationship was found between increased bronchial responsiveness and IgE. The geometric mean of "normal" values of IgE (*1 SD and *2 SD) of the Danish children and adolescents was 18 kU/l (*4.7, *18.2), suggesting that normal IgE values were within 330 kU/l. Measurement of IgE as the only screening for allergic disease is unreliable, as the predictive value of an elevated IgE in population samples was found to be 50%, whereas misclassification (1-specificity) of asymptomatic subjects as allergic because of an increased IgE was low (4%). In conclusion, total IgE is highly influenced by allergen skin reactivity. Further, this study suggests that normal IgE values were within 330 kU/l, although the range was wide.


Possible consequences of elimination diets in asymptomatic immediate hypersensitivity to fish.

The natural history of IgE antibodies to food without related symptoms is unknown. We have followed the progress of 7 children with various atopic diseases and asymptomatic immediate hypersensitivity to fish, treated with elimination diet in spite of full alimentary tolerance. During the diet period, between 24 and 113 months, all 7 patients presented immediate symptoms upon accidental exposure to or challenge tests with fish (skin symptoms in all 7 cases, digestive in 5, respiratory in 4, and anaphylaxis in 2), which differed from those related to atopic diseases previously present. The levels of fish-specific IgE (prick test, RAST) remained unchanged or were increased. These findings suggest that during elimination diet, and perhaps due to minimal and hidden contact with the allergen, the patients' degree of sensitization may increase, turning an asymptomatic into a symptomatic immediate hypersensitivity.


Comparison between two different assays for measurements of allergen-specific IgE and skin prick test in the diagnosis of insect venom allergy.

Forty-one patients stung by wasp and 29 by bee were evaluated by comparing the correlation between skin prick test (SPT), Phadebas radioallergosorbent test (P-RAST) and Magic Lite SQ Specific IgE assay (LIA). All patients had had a systemic reaction to insect sting. In the patients stung by bee we found agreement between SPT and P-RAST, and SPT and LIA. Similarly, there were no significant differences in sensitivity between P-RAST and LIA (p > 0.05). In patients stung by wasp, SPT was found to be more sensitive than P-RAST. There were no differences between SPT and LIA or between P-RAST and LIA.


Damp housing and adult respiratory symptoms.

The relationship between home dampness and adult respiratory symptoms was investigated using data from a parent-administered questionnaire on childhood respiratory symptoms that also included questions on parental respiratory symptoms. Questionnaires were returned by the parents of 3344 children living in the town of Helmond, The Netherlands. The response was 73%. Home dampness was characterized by reports of damp stains or mould growth on indoor surfaces and was reported by 23.6% and 15.0% of the study population, respectively. Of the homes, 25.4% had dampness and/or mould. Information about respiratory symptoms was collected for the mothers and fathers of a population of 6-12-year-old schoolchildren. Symptoms analysed were cough, phlegm, wheeze, asthma, and allergy to pollen or house dust. Cough and phlegm in both men and women were found to be strongly associated with living in a damp home. Weaker associations were found for wheeze and asthma, and there was little association between living in a damp home and allergy to pollen or house dust. Current smoking was strongly associated with cough, phlegm and wheeze in both men and women. Smoking was inversely associated with allergy to pollen or house dust, suggesting that allergic subjects do not start smoking, or give up the habit. The results suggest that the association between home dampness and respiratory symptoms previously reported for children also applies to adults. Suggested mechanisms include exposure to biological contaminants produced by fungi or house dust mites, but it has not yet been documented to what extent these exposures are responsible.(ABSTRACT TRUNCATED AT 250 WORDS)


Aeroallergen analyses and their clinical relevance. II. Sampling by high-volume airsampler with immunochemical quantification versus Burkard pollen trap sampling with morphologic quantification.

A comparison was made between the amount of airborne pollen collected by Burkard airsampler and the allergenic activity of particles trapped on glass fibre filters in an Accu-Vol high-volume airsampler. The comparison was made throughout the pollen seasons 1986 to 1989. Both airsamplers were operated 24 h a day. They were placed less than 5 m apart, and estimation of the pollen amount was made on a day-to-day basis during the pollen seasons, and on a weekly basis outside the seasons. The occurrence of the 3 clinically most important allergenic types of pollen, birch, grass, and mugwort, was analysed, and close correlations between the 2 sampling techniques were found (rs 0.5-0.8, p < 0.001). The detected range of counted pollens/m3 was: birch 0-1075, grass 0-156, and mugwort 0-44. By immunochemical analysis we found the corresponding amounts to be 0-80, 0-8, and 0-1 SQ-U/m3, respectively. Pollen counts and immunochemical estimation were compared with the symptom score recordings of allergic persons for birch season 1989 and for grass seasons 1986, 1988, and 1989. A close correlation was found for both sampling techniques for the grass seasons in 1986 and 1989 (rs 0.51-0.61, p < 0.001-0.0001), but a less significant correlation was found for the 1988 grass season, and for birch in 1989 (rs 0.24-0.34, p < 0.001-0.05).


Polyunsaturated fatty acids in plasma, red blood cells and mononuclear cell phospholipids of patients with atopic dermatitis.

Recent studies of polyunsaturated fatty acids (PUFA) in plasma and blood cell components of patients with atopic diseases have indicated disordered fat metabolism as linoleic acid (18:2n-6) tends to be increased while the more unsaturated fatty acids, such as gamma-linolenic acid (18:3n-6) and arachidonic acid (20:4n-6) are present in decreased amounts. To further clarify these abnormalities, we examined the PUFA content in phospholipids derived from plasma, red blood cells and mononuclear cells (MNC) in patients with atopic dermatitis. In plasma no significant differences were found between patients and controls. In red blood cells dihomo-gamma-linolenic acid (20:3n-6) was reduced in eczema patients, as compared with controls. The most significant findings in eczema patient MNC were reduced ratios of 20:4n-6/20:3n-6 in total lipids and in phosphatidyl ethanolamine (PE) and of 20:4n-6/18:2n-6 in both total lipids, phosphatidyl choline (PC) and PE. These findings indicate a disordered fatty acid metabolism in MNC of patients with atopic dermatitis. It is possible that these changes in the fatty acid profile of MNC may account for some of the immunological abnormalities seen in these patients.


Neonatal IgE levels and three different blood sampling techniques.

Comparison was made of IgE and IgA levels in aspirated and gravity-collected cord blood (CB) from the umbilical vein and in capillary blood samples collected on the 4-5th day of life among 21 infants with atopic heredity. The IgA levels, but not the IgE levels, were significantly (p < 0.001) lower at days 4-5 of life than at delivery. Further, there were significantly (p < 0.05) more infants with decreasing IgA levels (20/21; 95%) than IgE levels (9/15; 60% of those with detectable IgE, i.e., > or = 0.125 kU/l). These observations, together with the highly significant correlation observed between IgE in aspirated CB samples and at 4-5 days of age, suggest active IgE synthesis during the prenatal and postnatal periods. Contamination of CB with maternal blood, defined as an increased CBIgA level (> or = 14.1 micrograms/ml), was found in 3 (14%) CB samples, all of which were gravity-collected. Of 4 CB samples (gravity-collected) with elevated IgE (i.e., > or = 0.9 kU/l), 2 had suspected maternal contamination. Therefore, aspiration of CB or capillary collection at 4-5 days of age should be preferred for allergy prediction. If gravity collection is used, contamination should be investigated by determining IgA in all CB samples with IgE concentrations exceeding the cut-off point.


Ovalbumin aerosol challenge in actively sensitized guinea pigs: relationship between airway microvascular leakage and airflow obstruction.

Airway inflammation is a common feature of asthma, and one of the cardinal features of inflammation is increased microvascular permeability. We investigated the characteristics of inhaled ovalbumin challenge-induced airflow obstruction and airway microvascular leakage in vivo in mechanically ventilated guinea pigs actively sensitized to ovalbumin. A method was used to quantify both airflow obstruction and airway microvascular leakage in order to investigate the relationship between these 2 pathophysiological features in the same animal. Airway microvascular leakage was assessed by Evans blue dye extravasation into airway tissues. Actively sensitized guinea pigs developed both acute airflow obstruction (increased lung resistance and reduced dynamic lung compliance) and Evans blue dye extravasation in response to exposure to aerosolised ovalbumin. Evans blue dye extravasation was preferentially distributed in the distal airways and correlated with airflow obstruction. The results show that inhaled allergen induced both acute airflow obstruction and airway microvascular leakage.


Evaluation of antihistamine-related daytime sleepiness. A double-blind, placebo-controlled study with terfenadine.

The daytime sleepiness potentially associated with antihistamines was evaluated by the multiple sleep latency test (MSLT) in a study comparing terfenadine with placebo. According to a double-blind, randomized, cross-over design, 12 healthy men were given either 120 mg terfenadine or placebo once daily in the morning, for 3 consecutive days with a 5-day interval. EEG-polygraphic recordings were made each study day at 9:30 and 11:30 a.m., and 1:30, 3:30, and 5:30 p.m., and the tendency to fall asleep was measured. All mean stage-1 sleep latencies throughout the study failed to show any significant difference between terfenadine and placebo. Accordingly, psychomotor performance assessed by visual and auditory reaction time did not change after treatment. The results of this study confirmed that terfenadine does not induce daytime sleepiness as objectively measured by MSLT.


Characterization of antigens and allergens of date palm (Pheonix dactylifera) pollen. Immunologic assessment of atopic patients by whole extract and its fractions [corrected].

Antigenic and allergenic components of date palm (Phoenix dactylifera) pollen were investigated to observe their effects on the skin test reactivity, lymphocyte blastogenesis and cytokine production in atopic and healthy individuals. Date pollen extracts were fractionated using SDS-PAGE and Sephacryl S-200 gel filtration. Western blotting of SDS-PAGE separated components with antiserum raised against whole pollen extract in rabbits revealed at least 22 immunoreactive bands ranging in molecular weight between 12 and 94 kD. The immunogenicity of the pollen extract was further confirmed by strong positive reactions in ELISA and Ouchterlony's double diffusion tests. Immunoblot analyses revealed IgG and IgE reactive components (14-94 kD for IgG and 12-90 kD for IgE) in the skin test-positive patients' sera against whole pollen extract. Fifteen of 60 atopics reacted positively to either whole or some fractions of date pollen extract when skin tested. In response to whole or components of date pollen extract atopic patients showed differential peripheral blood lymphocyte (PBL) proliferative response and cytokine (IL-2, IL-4) production when compared with PBL of normal subjects. Our findings strongly suggest that date palm pollen should be considered a reaginic component and should be included in the battery of allergens for determining the allergic status of atopic patients, particularly in those parts of the world where the date palm is grown commercially.


Effect of an allergy prevention programme on incidence of atopic symptoms in infancy. A prospective study of 159 "high-risk" infants.

A total of 105 "high-risk" infants born in 1988 were studied prospectively from birth to 18 months of age. The infants were recommended breastfeeding and/or hypoallergenic formula (Nutramigen or Profylac) combined with avoidance of solid foods during the first 6 months of life. All mothers had unrestricted diet. Avoidance of daily exposure to tobacco smoke, furred pets and dust-collecting materials in the bedroom were advised. This prevention group was compared with a control group consisting of 54 identically defined "high-risk" infants born in 1985 in the same area. All infants had either severe single atopic predisposition combined with cord blood IgE > or = 0.5 KU/l or biparental atopic predisposition. The control group had unrestricted diet and was not advised about environmental factors. Apart from the prevention programme and year of birth the prevention group and the control group were comparable. The parents were highly motivated and compliance was good. The rate of participation was 97%, and 85% followed the dietary measures strictly. The cumulative prevalence of atopic symptoms was significantly lower at 18 months in the prevention group (32%), as compared with the control group (74%) (p < 0.01), due to reduced prevalence of recurrent wheezing (13% versus 37%; p < 0.01), atopic dermatitis (14% versus 31%; p < 0.01), vomiting/diarrhoea (5% versus 20%; p < 0.01) and infantile colic (9% versus 24%; p < 0.01). The cumulative prevalence of food allergy was significantly lower in the prevention group (6% versus 17%; p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)


Biomolecular regulation of the IgE immune response. I. Cell-associated IgE and in vitro IgE synthesis.

Several cell types, including mast cells, basophils, macrophages/monocytes, lymphocytes, platelets and eosinophils, may bind or contain IgE. To investigate the source of cell-associated IgE and its relation to spontaneous IgE synthesis, peripheral blood mononuclear cells from allergic and non-allergic donors were examined. Using a combination of different cell fractionation techniques and varying methods for extraction of cell-associated IgE, data were obtained indicating that monocytes constitute a major source of cell-associated IgE in human blood. The amount of cell-associated IgE in peripheral blood mononuclear cells from allergic and non-allergic donors varied more than 100-fold but correlated closely to the level of serum IgE (r = 0.84, p < 0.001, n = 38). Spontaneous and mitogen-induced in vitro syntheses of IgA, IgE and IgG were compared for allergic and non-allergic donors. Only one donor with very high serum IgE demonstrated spontaneous or mitogen-induced in vitro IgE synthesis despite synthesis of IgA and IgG.


Anaphylactic shock by rupture of hydatid hepatic cyst. Follow-up by specific IgE serum antibodies.

Total and specific serum IgE antibodies were estimated in a 68-year-old woman with anaphylactic shock due to spontaneous rupture of hydatid cyst of the liver. After she had recovered, an abdominal ultrasonography showed a cyst, 10 x 15 cm, in the right hepatic lobe. The cyst was surgically removed. Antihydatid IgE in the acute phase and periodically after surgical intervention, determined by Phadezym RAST, Pharmacia, and Pharmacia CAP system (a new solid-phase immunoassay, fully automated, for the titration of specific IgE with greater sensitivity in the detection of low IgE antibody levels), showed decreasing antihydatid IgE antibodies on day 10 after surgical intervention and may thus serve to monitor the evolution of hydatid disease.


Occupational pharyngitis associated with allergic patch test reactions from acrylics.

A female dentist specialized in orthodontics repeatedly developed symptoms of pharyngitis at work. A chamber provocation test indicated that her symptoms were caused by acrylics. Prick tests with acrylics were negative, while patch tests were strongly positive although the patient had no skin symptoms. The relationship between the symptoms and the patch test results is discussed. It is suggested that type IV allergic reactions may be involved in symptoms of the upper respiratory tract.


A case of fallow deer allergy. Cross-reactivity between fallow deer and horse allergy.

We report the case of a 25-year-old housewife, a native of Mexico City, with rhinitis and asthma induced by exposure to fallow deer in an animal park close to her home. In the literature, we could find only one previous case. The patient presented a polyvalent IgE sensitization in prick skin tests and RAST to several animals' dander and epithelia, but RAST inhibition experiments showed a cross-reactivity only between fallow deer and horse allergen extracts.