Effect of anoxic preperfusion on ischemic myocardial injury in isolated rat hearts.

Anoxic perfusion prior to sustained ischemia (anoxic preperfusion), reportedly improves postischemic functional recovery of the heart, but its mechanism has not been well understood. The present study aimed to characterize the cardioprotective effects of anoxic preperfusion and its relationship to extracellular Ca++ levels. Following 10 min of aerobic perfusion, isolated rat hearts were assigned to a 10 min aerobic perfusion or to a 10 min anoxic perfusion. The hearts were then subjected to 30 min of global ischemia and 30 min of aerobic reperfusion. When the perfusate-free Ca++ concentration was 2.0 mM, postischemic recovery of left ventricular developed pressure was significantly improved by anoxic preperfusion (91.9 +/- 2.9% of baseline value vs. 50.5 +/- 12.9% after 30 min reperfusion in the controls). However, the improvement of postischemic ventricular function by anoxic preperfusion was abolished when perfusate Ca++ was reduced to 1.0 mM and the contractile function was rather suppressed during early reperfusion by anoxic preperfusion when the Ca++ level was 0.7 mM (87.5 +/- 11.8% vs. 115.6 +/- 13.9% after 10 min of reperfusion). On the other hand, lactate accumulation during the global ischemia was significantly less in anoxic preperfused hearts compared with untreated hearts both when perfusate Ca++ was 0.7 mM (61.3 +/- 5.1 vs. 85.9 +/- 6.8 mumol/g dry) and when it was 2.0 mM (43.8 +/- 2.0 vs. 140.3 +/- 14.1 mumol/g dry). The amount of myoglobin released after global ischemia was not different between untreated and anoxic preperfused hearts regardless of the perfusate Ca++ level. The results suggest that anoxic preperfusion does not reduce ischemic myocardial necrosis, but it attenuates myocardial stunning. That effect of anoxic preperfusion on the stunning is dependent on the extracellular Ca++ level and is not totally explained by suppression of ischemia-induced lactate accumulation.


Effect of L-carnitine on the cellular distribution of carnitine and its acyl derivatives in the ischemic heart.

The purpose of this study was to investigate the cellular distribution of carnitine and its acyl derivatives in the normal and ischemic myocardium, and the effects of exogenous 1-carnitine on this distribution and mitochondrial function in the ischemic dog heart. Under non-ischemic conditions, about 93% of the total cellular carnitine was located in the cytosolic compartment and 6.5% in the mitochondrial compartment. Sixty minutes of ischemia induced a decrease in the cytosolic free carnitine content, but caused the accumulation of long-chain acylcarnitine in the cytosolic and mitochondrial compartments. Treatment with 1-carnitine (30 or 100 mg/kg, i.v.) inhibited the mitochondrial accumulation of long-chain acylcarnitine. Free fatty acid (FFA) metabolism in the mitochondria differs from that in the cytosol. So, it is necessary to investigate the changes in FFA metabolism in both of these cellular compartments. Our results suggest that 1-carnitine has a protective effect on the ischemic heart by selectively reducing mitochondrial accumulation of long-chain acylcarnitine.


The role of calcium activated neutral protease on myocardial cell injury in hypoxia.

The aim of this study was to investigate the correlation between hypoxic myocardial cell injury and intracellular protease activity. Cardiac myocytes were isolated from neonatal rat hearts and cultured in Eagle's modified minimum essential medium. Myocytes were incubated in hypoxic conditions for 6 hours. The cell death rate during hypoxia rose to 80% after 6 hours. Extracellular protease activity was elevated to 4 units during hypoxia, much higher than the 0.7 units in aerobic states at 6 hours. This extracellular protease activity in hypoxic conditions was markedly inhibited by leupeptin and EDTA, and weakly inhibited by the cysteine protease inhibitor, NCO-700, but phenylmethyl sulfonyl fluoride did not inhibit the protease activity. To identify the protease activated during hypoxia, calpain-specific inhibitors were added to the incubation mixture. Calpain inhibitor 1 and calpastatin, an endogenous selective calpain inhibitor, markedly inhibited extracellular protease activity during hypoxia. NCO-700 also inhibited intracellular protease activity. NCO-700 reduced hypoxic cell death to 30% after 6 hours of hypoxygenation. These observations indicate that calpain is activated during hypoxia and leads to irreversible cell membrane degradation after 6 hours of hypoxygenation.


Histochemical study of calmodulin in dog myocardial ischemia and sudden cardiac death.

The distribution of calmodulin was investigated in dog myocardium after coronary artery occlusion by an immunoperoxidase technic and compared with the distribution of myoglobin and the findings of hematoxylin-eosin (H-E) staining. After 60 min or more of coronary artery ligation, calmodulin diffused clearly from myocardium in the region of hypereosinophilia (H-E) or stained intensely in regions of a contraction band or hydropic appearance. Similar findings were observed in the myocardium of cases of sudden cardiac death. The intense staining for calmodulin would reflect the association of calmodulin with membranes in response to the calcium overload that plays an important role in myocardial injury. Calmodulin staining provided more information than myoglobin staining, which only detected diffusion from necrotic cells. This method would be useful to elucidate the implications of calcium and calmodulin during the development of myocardial injury.


Torsade de pointes induced by hypocalcemia in a postoperative patient with thyrotoxicosis.

A 29-year-old woman with a long-term history of Graves' disease was admitted for thyroidectomy. Torsade de pointes occurred after the subtotal thyroidectomy. The level of her serum calcium was lower than normal. After administration of calcium gluconate intravenously, torsade de pointes disappeared and was no longer recorded. It is assumed that her torsade de pointes was caused by hypocalcemia as a complication of subtotal thyroidectomy.


[Analysis of the electrical charge of albumin in idiopathic nephrotic syndrome by isoelectric focusing].

The state of the electrical charge of serum and urinary albumin was investigated in both the nephrotic and remission stage of idiopathic nephrotic syndrome (INS), using isoelectric focusing (IEF). 1) Both a b2 band (a main albumin band appearing at the site of isoelectric point: pI 4.7), and a b3 band (a more anionic albumin band than the b2 band) were detected commonly in all samples of urine and serum of INS patients in nephrotic and remission stages and of healthy volunteer controls even if the applied albumin in urine and serum amounted to 20 micrograms or 100 micrograms. 2) When applied albumin amounted to 20 micrograms, b1 bands (less anionic albumin bands than the b2 band) were detected between pI 4.7 and pI 6.5 in urine and in both serum and purified albumin fractionated from serum of INS patients in the nephrotic stage. However, b1 bands were not detected at all in the urine and serum of either INS patients in remission stage and healthy volunteer controls. 3) When applied albumin amounted to 100 micrograms, b1 bands were detected also in serum of healthy volunteer controls. From these results, it was confirmed that less anionic albumin existed also in the serum of healthy volunteer controls although the amount was extremely small.(ABSTRACT TRUNCATED AT 250 WORDS)


[Cu, Zn-superoxide dismutase, glutathione peroxidase location in kidney of IgA nephropathy].

To study the role of reactive oxygen species (ROS) in chronic renal disease, we studied the localization of Cu, Zn-Superoxide dismutase (SOD) and Glutathione peroxidase (GSH-Px) in glomeruli of patients with IgA nephropathy by immunohistochemical method. Thirty three kidney specimens were used consisting of 28 IgA nephropathy and, normal parts of the 5 resected kidneys with renal tumors as controls. To evaluate the change of renal function and renal histological grade, creatine clearance (Ccr) and histological grade were assessed at the time of biopsy. In normal kidney, Cu, Zn-SOD and GSH-Px was localized in tubular cells, and not in glomeruli. In the kidney with IgA nephropathy, Cu, Zn-SOD and GSH-Px were detected in epithelial side of the glomerular capillary wall in addition to the tubular cells. The positive correlation was observed between the glomerular localization of Cu, Zn-SOD and that of GSH-Px. As for the relation between the extent of localization of these enzymes and clinical findings at the time of biopsy, the following results was obtained. When Cu, Zn-SOD and GSH-Px was strongly stained in glomeruli, histological change of glomeruli was milder. These results suggest that Cu, Zn-SOD and GSH-Px have the beneficial actions for renal function as anti-oxidative factors.


[Effect of oral adsorbent (AST-120) in the rat model of chronic renal failure induced by adriamycin].

The effect of AST-120 was examined in the rat model of CRF induced by adriamycin (ADM), which is known to induce focal glomerular sclerosis (GS). ADM (2mg/kg) was injected intravenously twice at a 3-wk interval. After 14 wks, rats were paired with control (C) and AST-120 (A) groups according to levels of BUN and proteinuria. Then, the rats were fed regular rat chow with (A, n = 10) or without (C, n = 10) AST-120. After 28 wks, there were more GS in C. Averaged sclerosis index (SI, 0-4 scale) in C was 1.97 (0.94-3.22), while 1.61 (0.60-2.97) in A. When GS was advanced in C (SI > 2.0), largely ameliorated SI was noted in A (2.61 vs. 1.97, C vs. A, p < 0.05 by paired W-test, n = 5 each). Also, in these rats, BUN, serum creatinine and Ht were all improved in A (p < 0.05). Thus, AST-120 was effective in CRF rats induced by ADM when uremia was advanced. The data also indicates that a reduction of uremic toxins could improve glomerular histology and renal function in CRF.


[Alterations of gluconeogenesis by ischemic renal injury in rats].

This study was designed to determine changes in one of metabolic functions, gluconeogenesis after ischemic renal injury. Right kidneys of SD rats were removed and a vascular clamp was placed across the left renal artery and vein for 0, 10, 30, 60 and 90 min. On 1, 3 and 7 days after the treatment, tubule suspensions were prepared by collagenase treatment of left kidneys and incubated with or without 2 mM pyruvate or malate aerobically. After the incubation, glucose contents were assayed photometrically. Serum creatinine was also determined. In addition, morphological changes were observed under light microscopy to examine the relationship between metabolism and morphology. The tendency of increase of gluconeogenesis was observed on day 1 and 3 after 10, 30, 60 min of ischemic time. On the other hand, gluco-neogenesis decreased significantly on day 1 after 90 min treatment. In contrast, on day 1 and 3 after treatment, serum creatinine levels showed no difference from control at the groups of 10 and 30 min ischemia. Whereas it rose significantly at the group of 60 min ischemia, showing a different tendency from that of the increase of gluconeogenesis. Moreover, morphologic damage was observed on day 1 and 3 after ischemia of 30 and 60 min. The morphologic damage was found more advanced in the corticomedullary region than those of the cortex which has the high gluconeogenic activity and which thus showed relatively limited damage. These results suggest that renal gluconeogenesis is relatively insusceptible to ischemic injury.(ABSTRACT TRUNCATED AT 250 WORDS)


[Effects of age, renal diseases and diabetes mellitus on the renal size reduction accompanied by the decrease of renal function].

Renal size reduction accompanied by the decrease of renal function was evaluated by ultrasonography in 30 normal controls, 45 patients with chronic renal diseases (CRD) and 22 patients with diabetic nephropathy (DN). In controls, significant positive correlation was observed between sectional areas of right kidney and creatinine clearance (Ccr) (r = 0.794, p < 0.001), suggesting that the decrease of renal function due to aging was accompanied by the renal size reduction. Significant correlation was also found between the size and Ccr in CRD (r = 0.814, p < 0.001) and DN (r = 0.640, p < 0.01). No significant difference was observed between controls and CRD in the reduction rate of renal size per unit change of Ccr, which suggested that the renal size reduction accompanied by the decrease in Ccr was the same in controls and CRD. In contrast, in DN, renal size reduction accompanied by the decrease in Ccr was smaller than controls or CRD. When renal sizes were compared in patients, whose Ccr were equal or less than 20 ml/min, renal sizes were significantly larger in DN than CRD (p < 0.001). The duration of illness from the onset of proteinuria was longer in CRD than DN (13.5 years and 4.7 years, respectively). The difference of renal sizes, however, can not be fully explained by the differences in the length of illness, since the renal size was larger in DN than CRD even when we compared the patients with the similar length of illness. In conclusion, renal size decreased with the reduction in the renal function in controls, CRD and DN.(ABSTRACT TRUNCATED AT 250 WORDS)


[Guanidino compounds and aliphatic monoamines in acute and chronic renal failure].

Small molecular weight uremic toxins, guanidino compounds and aliphatic monoamines, were measured in the serum of chronic and acute renal failure (CRF and ARF) patients. A close correlation was noticed between guanidinosuccinic acid (GSA) and serum urea nitrogen (BUN) and also between methylguanidine and serum creatinine (Cr) in nondialyzed and dialyzed CRF patients. The same relation was seen in ARF patients showing rapid change of metabolic conditions, which suggested the tight linkage between guanidino compounds and protein metabolites. On the other hand, dimethylamine (DMA) was related with Cr in CRF patients, however, not in ARF patients. Since the production of DMA from Cr is carried out mainly, but relatively slowly, by bacterias in the intestine, the rapid metabolic change of ARF may not affect DMA synthesis. Furthermore, the DMA synthesis from trimethylamine-N-oxide (TMA-N-O) was studied using liver homogenate. The liver homogenate produced DMA by adding TMA-N-O as substrate. However, the kidney homogenate could synthesize it even without substrate. Therefore, the kidney seems to be a major site of DMA production as well as the intestine.


[MCNS, which secondary developed into incidental IgA nephropathy--a case report].

There have been a number of case reports on nephrotic syndrome with histological findings of minimal change on light microscopy and mesangial IgA deposition on fluorescent microscopy. The pathogenesis of these cases is, however, yet to be clarified. Here, we report a case of minimal change nephrotic syndrome (MCNS) associated with IgA nephropathy, which developed later in the course of MCNS. The patient was 18 years old male with steroid-responsive nephrotic syndrome. First episode of proteinuria occurred when he was 4 years old. On the fourth episode of proteinuria, renal biopsy revealed minimal change on light microscopy and no evidence of deposition of immunoglobulins or complements on immunofluorescent and electron microscopy. On the fifth relapse of MCNS, microhematuria developed concomitantly with massive proteinuria. Renal biopsy, then, showed light microscopic findings of mild focal segmental glomurulonephritis. Significant mesangial IgA deposition was observed on immunofluorescence study. Electron microscopy revealed electron dense deposit in the mesangial and paramesangial area. The patient was well-responsive to steroid although microhematuria persisted after disappearance of proteinuria. We concluded that IgA nephropathy may have developed subsequently in the course of MCNS in our case.


[A case report of chronic tubulo-interstitial nephritis].

We report a case of 10-year-old boy with chronic tubulo-interstitial nephritis (TIN). He had febrile convulsion and received sodium valproate (VPA) treatment. 18 months later, he had developed Fanconi syndrome. On admission, he also had evidence of tubular and glomerular dysfunction. Renal biopsy revealed interstitial nephritis with linear tubular-basement-membrane deposition of IgG and C3 and dominant infiltration of CD4 positive cells in interstitium. Although there is not a positive proof of the etiology in the relationship between TIN and VPA, it is likely that VPA is a possible cause of chronic TIN from his past history.


[Tissue renin content in superficial, midcortical, and juxtamedullary afferent arterioles in rabbits].

Tissue renin content within the kidney decreases from outer to inner cortex. However, it is not known whether this gradient is due to a decrease in the number of afferent arterioles from the outer to inner cortex or the decrease in renin content per afferent arteriole. Furthermore, it is still controversial whether sodium depletion increases or decreases this gradient. According to Taugner et al., sodium depletion induces the extension of renin positive part of afferent arterioles from vascular pole toward interlobular artery. Since the length of extension may differ among superficial, midcortical, and juxtamedullary afferent arterioles, the observed gradient may vary depending on whether the entire afferent arteriole or only the vascular pole is examined. In the present study, we microdissected the entire afferent arterioles from superficial, middle, and juxtamedullary cortex of rabbit kidney, and examined tissue renin content. We studied: 1. whether tissue renin content per afferent arteriole decreases from the outer to inner cortex. 2. whether sodium depletion affects the gradient of tissue renin content within the cortex. In result, we reached the conclusions, as follows: 1. Tissue renin content per afferent arteriole decreases steeply from superficial to midcortical to juxtamedullary afferent arterioles. 2. The absolute difference in renin content among the three types of afferent arterioles becomes greater during sodium depletion. The internephron heterogeneity of tissue renin content may contribute to functional heterogeneity.


[Renin release from microdissected superficial, midcortical, and juxtamedullary afferent arterioles in rabbits].

Though renin release from a single superficial afferent arteriole has been studied extensively, there is no report on renin release from a single midcortical or juxtamedullary afferent arteriole. In the present study, we microdissected the entire afferent arterioles from superficial, middle, and juxtamedullary cortex of rabbit kidney, and examined renin release from a single afferent arteriole. In result, we got the following conclusions. 1. Basal renin release per afferent arteriole decreases steeply from superficial to midcortical to juxtamedullary afferent arterioles during both normal and low sodium intake. 2. Isoproterenol (1.6 x 10(-4)M) significantly stimulates renin release from all three types of arterioles on either diet; however, only in the superficial arterioles is the increase (delta) greater with dietary sodium restriction. These findings indicate substantial heterogeneity of basal and isoproterenol-stimulated renin release, and response to chronic sodium depletion.


Cortical area related to lens accommodation in cat.

Lens accommodation was evoked by microstimulation in the lateral suprasylvian (LS) area in cats. The accommodative response was monitored continuously with an infrared optometer. The low threshold areas related to lens accommodation were located in the lower parts of the medial banks of the middle suprasylvian sulcus from A1 to A4, and also in the fundus of the sulcus at A8 in the stereotaxic coordinates. The latency of the onset of the accommodative responses evoked by stimulating the caudal area (A1-A4) was shorter than that evoked by stimulating the rostral area (around A8). Electrical stimulation was also attempted at the subcortical area in order to study the output pathway from the LS area. It was determined that the low threshold sites in the LS cortex of A1-A4 extend rostrally along the lateral ventricle in the brainstem, then ventrally into the midbrain. These findings suggest that there are two cortical areas related to lens accommodation: caudal and rostral, and the caudal accommodation area may provide the output signal for the subcortical system.


Quantitative and morphometric studies of age-related changes in human ciliary muscle.

The age-related changes in ciliary muscles were studied morphologically in 20 human eyes ranging from 3 months to 90 years of age. The meridionally cross-sectioned area and the volume of ciliary muscles increased with age until 70 years, but then decreased. The circular fiber in the ciliary muscle was undeveloped in the infantile eye. However, it continued to develop until about 70 years of age, and then decreased. The connective tissue in the ciliary muscle showed a proportional age-related increase. Over 71 years of age the proportion of connective tissue became larger than that of the muscle fiber. The number of nuclei in the ciliary muscle was maximum in eyes between 21 to 40 years of age, and subsequently there was a continuous and distinct decrease in the circular fiber with age. The age-related increase of connective tissue and decrease of nuclei in the ciliary muscle together with the decreasing circular fiber suggested a possibility of atrophy in the ciliary muscle with age-related deterioration of accommodation.


Histological and histochemical studies on developing ciliary body in eye of ICR mouse.

Histological and histochemical studies have been made on the microscopic structures of the ciliary body from the developing eyes of both pre- (on day 13, 16 and 18 of gestation) and postnatal (on day 1, 5, 10, 14 and 84) mice of the Jcl:ICR strain and on the acidic glycoconjugates contained in the ciliary body tissues of these animals. As the staining procedures of choice, a hematoxylin-eosin procedure and a sensitized high iron diamine method were employed. A nitrous acid procedure was used in combination for some tissue sections, prior to the sensitized diamine method, to aid in the identification of sulfated glycoconjugates. Both the partes optica and caeca retinae could be identified histochemically as early as day 13 of gestation, whereas these parts could not be histologically distinguished from each other at day 16 of gestation. The ciliary folds were detected first in the external layer at day 16 of gestation and subsequently in the internal layer 2 days later. The heparan sulphate proteoglycan observed not only in the thick basement membrane but also in the intra- and intercellular spaces of the internal layer was localized in a distribution pattern which prevented the occurrence of configurational discrepancies between the epithelial cells lining the layer because of the formation of ciliary folds.


Recombinant human epidermal growth factor and corneal neovascularization.

With a view toward possible future clinical application, we investigated whether recombinant human epidermal growth factor (hEGF) could induce corneal neovascularization. Ethylene-vinyl-acetate copolymer slow-release pellets containing either 250 ng, 500 ng or 1 microgram of hEGF or 250 ng of bovine serum albumin (BSA) were implanted into rabbit corneal stroma, and the corneas were examined by slitlamp biomicroscope for 3 weeks. The results indicated that less than 1 microgram of hEGF per pellet did not induce neovascularization in the cornea. However, when pellets containing 250 ng of basic fibroblast growth factor (bFGF) were implanted, corneal neovascularization toward these pellets occurred within 10 days. The same phenomenon occurred toward the 250 ng hEGF pellets embedded in the ipsilateral or contralateral cornea of the same animal, but was significantly less severe. When a pellet containing 250 ng bFGF was intramuscularly implanted in the animal's back, similar neovascularization was observed toward the pellets containing hEGF implanted in the same animal's cornea, but not toward implanted pellets containing BSA. These results suggest that less than 1 microgram of hEGF cannot initiate corneal angiogenesis, but can promote new vessel formation if the limbal vasculature is activated by a sprouting signal from a certain substance as trace amounts of bFGF.


Keratoepithelioplasty in rat: development of a model and histological study.

A model for keratoepithelioplasty (KEP) was developed using the Lewis rat, and histological studies were performed using this model. The entire corneal epithelium was removed mechanically and a 1.5-mm width of the conjunctiva including the limbus was excised. An oval corneal lamellar graft (3 x 1.5 mm) with an intact epithelium taken from another Lewis rat was transplanted on the denuded limbus. Biomicroscopic observations showed much less vascular invasion in the part of the cornea adjacent to the lenticule than in other parts of the cornea, and the cornea remained clear adjacent to the lenticule. Histologically, a few vessels were observed in the corneal stroma under the lenticule. Epithelial cells on the lenticule specimens showed histological characteristics of the corneal epithelium. These findings indicate that one of the functions of KEP is to block neovascularization in the newly developing corneal epithelium by transplanting the lenticule between the corneal epithelium and conjunctival vessels. The present study also confirmed that this model is useful in the research of the pathophysiological mechanism of KEP.


Alteration of lens disulfide bonds in newly developed hereditary cataract rat.

A newly developed hereditary cataract rat named Shumiya Cataract Rat (SCR) is introduced. The lens opacity manifests spontaneously in the nuclear and perinuclear portions of the lens in this model at 11 weeks of age. Raman optical dissection studies reveal that lens protein disulfide bonds are considerably decreased in the SCR opaque lens nucleus. This tendency is also detected in the precataractous stage. The simultaneous increase of lens protein sulfhydryl groups is observed in the affected lens nucleus. The glutathione disulfide (oxidized glutathione) level, on the contrary, is elevated in the SCR opaque lens, whereas the glutathione sulfhydryl (reduced glutathione) level is decreased. It is suggested that the impaired formation of protein disulfide bonds is related to lens opacification in a hereditary manner.


New inferior retinal detachment after scleral buckling procedure with intraocular gas injection.

In a series of 72 rhegmatogenous retinal detachments treated by scleral buckling procedure with or without intraocular gas injection, 5 patients showed a subsequent inferior retinal detachment in the operated eye early in the postoperative period. All 5 eyes had been injected with air or sulfur hexafluoride intraoperatively or postoperatively, and had vitreoretinal adhesions such as lattice degeneration in the inferior equatorial fundus. To investigate the factors involved in the development of the new inferior retinal detachment, the data on the 72 eyes of retinal detachment were analyzed. Intraocular gas injection, inferior vitreoretinal adhesion, and the volume of injected gas were the significantly associated factors (P < 0.05). It was suggested the intraocular gas bubble could produce traction on the site of inferior vitreoretinal adhesion, leading to new inferior retinal detachment.


Lymphatic sinus-like structures in choroid.

Lymphatic sinus-like structures were demonstrated in the choroid of the monkey eye by transmission and scanning electron microscopy. These lymphatic sinus-like structures were lined by fibroblast-like cells with large intercellular gaps. When the specimens were viewed by scanning electron microscopy, the surface morphology of the fibroblast-like cells was similar to that of the endothelial cells of blood vessels or lymphatic vessels. Some fibroblast-like cells possessed intracellular fenestrations which varied in size, number and distribution. It is suggested that the lymphatic sinus-like structures here observed might play a role in the drainage of fluid from the choroid.


Immunohistological study of subretinal membranes in age-related macular degeneration.

An immunohistological study was performed on 6 specimens of subretinal membranes obtained surgically from patients suffering from age-related disciform macular degeneration. using immunoperoxidase procedures, we found in those membranes large amounts of IgG, IgA and IgE as well as C1q, C3c and C3d complement components diffusely distributed in the connective stroma and within the new blood vessel walls. Moreover, subretinal membranes contained numerous isolated HLA-DR- and -DQ-expressing cells, including glial, pigment epithelial and vascular endothelial cells. Monoclonal antibodies to immunocompetent cells disclosed only rare B and natural killer lymphocytes or suppressor-cytotoxic T cells, as well as some monocytes. These results show that immune phenomena are involved in proliferative changes associated with subretinal neovascularization. In addition, they suggest there are interactions between the immune system and peptide growth factors.


Intraocular manifestations of systemic sarcoidosis.

The incidence of intraocular manifestations was studied in 159 patients with systemic sarcoidosis. Eighty-seven patients (54.7%) who presented ocular lesions suggestive of sarcoidosis as an initial manifestation were diagnosed after a systemic survey. Seventy-two patients (45.3%) had chest signs or symptoms and were referred to ophthalmic examination during a diagnostic survey. Of the 159 patients, 126 (79.2%) showed intraocular involvements at diagnosis. In these patients with ocular involvements, iritis was the most frequent lesion, being seen in 74.7%. Gonioscopic examinations revealed trabecular nodules and tent-like peripheral anterior synechia in 61.2 and 54.5% of the patients respectively. Retinal perivasculitis and spotty retinochoroidal exudates were seen in 67.3 and 53.9% of the patients respectively. The data indicated the presence of intraocular lesions in a significant number of patients with sarcoidosis. These findings emphasize that all patients with systemic sarcoidosis need a thorough eye examination. This ocular examination should include gonioscopy.


Molecular basis of congenital color vision defects in Chinese patients.

Applying Southern blot hybridization, the structures of the red pigment gene (RPG) and the green pigment gene (GPG) were analyzed in 43 Chinese patients with red-green color vision defects, including 3 female cases of deuteranopia. The same analysis was carried out in 4 normal relatives and 3 carriers from 3 affected families, as well as in 11 normal controls. Among the 43 patients, abnormalities of the RPG were detected in all 19 protans, and abnormalities of the GPG were found in 14 of the 24 deutans. In about 80% of the protans and deutans, an alteration of exon 5 in RPG or GPG was discovered. All 19 protans had anomalous RPG and in one protan the normal RPG was replaced by a 5' red-3' green hybrid gene. However, no protans showed deletion of the whole RPG. Some deutans had no GPG; some had a 5' green-3' red hybrid gene with or without the GPG. The exon 5 of RPG and GPG was amplified by polymerase chain reaction (PCR) and the amplified fragments were further analyzed by RsaI digestion. The results of PCR were identical to those of nucleic acid hybridization. PCR will be a useful tool in prenatal diagnosis and genetic counseling.


[Prediction formulas for pulmonary function tests expressed in linear and exponential form for healthy Japanese adults].

We studied 21 parameters of pulmonary function in 172 healthy Japanese adult smokers and non-smokers ranging from 18 to 83 years of age. Prediction formulas for each parameter were calculated in both linear and exponential form using multiple regression analysis with regard to sex, age, height and weight. The exponential form was superior to the linear form for V25, V50, PEF, FVC, VC, FEV1.0, FEV1.0%, TLC, DLCo and DL/VA, namely, the parameters whose predictive value decreases with aging. In particular for V25, only the exponential form of the predictive formula could be applied for subjects with advanced age. For PMI, LCI, IDI, pulmonary N2 clearance delay, and single breath delta N2, indices for unevenness of intrapulmonary gas distribution, there has been no previous report about their predictive formulas and ours is the first. These predictive formulas all showed increasing values with aging, and showed higher predictive values in females than in males, except for delta N2. These parameters require further study with respect to their normal value ranges and differences between males and females.


[Elemental analysis of hilar and mediastinal lymph nodes in idiopathic pulmonary fibrosis].

Elemental analysis of hilar and mediastinal lymph node tissues was performed to determine whether some inhaled atmospheric elements are implicated in the pathogenesis of idiopathic pulmonary fibrosis (IPF). IPF was divided into two types; typical and atypical, according to our criteria. Lymph nodes were selected as the study material rather than lung tissue, because inhaled elements are concentrated in the hilar and mediastinal lymph nodes, and increase in lung weight due to fibrosis may influence the estimated values of element per unit weight of lung tissue. The hilar and mediastinal lymph nodes collected from 40 IPF cases and 43 non-IPF control cases were examined to determine the concentration of 13 elements in 100 mg dry tissue, using the X-ray fluorescent analysis method. For aluminium, 50 mg dry tissue was examined by an atomic absorption analysis method. Among the 14 elements, Ni in IPF lymph nodes showed a significantly higher level than in control nodes (mean +/- SD: 8.2 +/- 21.3 ppm versus 1.1 +/- 2.1 ppm, respectively. p < 0.01). No difference in each of the examined elements was noted between smokers and non-smokers or between typical and atypical IPF cases. Exogenous elements such as Ni may play a role as triggering substances in the pathogenesis of IPF.


[Effects of respiratory tract infections and antibiotic therapy on NADPH oxidase activity].

The superoxide generation of neutrophil NADPH oxidase was investigated in healthy subjects, patients with respiratory tract infections, and patients receiving effective antibiotic therapy. In adults, oxidase activity significantly increased during respiratory tract infections and decreased after treatment with effective antibiotics. In the elderly, no significant increase in oxidase activity was observed during respiratory tract infections, while the activity significantly decreased after therapy. Increases in white blood cell counts, neutrophil counts and C-reactive protein values in the elderly during respiratory tract infections were less marked than those in adults. These abnormalities in both adults and the elderly were restored to within normal limits after antibiotic therapy. In in vitro experiments, antibiotics, such as imipenem, ceftazidime and cefoperazone, at each therapeutic dose did not inhibit the superoxide generation of NADPH oxidase. These results suggest that in the elderly, defense activity against infections may be suppressed, and that these antibiotics may normalize neutrophil NADPH oxidase activity as a result of their bactericidal action and a possible biological action to normalize the peri-neutrophil environment of the body.


[Tumor associated carbohydrate antigens in bronchoalveolar lavage fluid in patients with diffuse panbronchiolitis].

It is known that tumor associated carbohydrate antigens are significantly increased in the serum of patients with diffuse panbronchiolitis (DPB). We investigated carbohydrate antigens (SLX, CA19-9) in bronchoalveolar lavage fluid (BALF) obtained from 24 patients with DPB. The concentrations of SLX and CA19-9 were significantly higher in BALF from patients with DPB than those from healthy subjects (7 cases) and patients with pulmonary sarcoidosis (16 cases). No significant correlation was observed between either SLX or CA19-9 concentrations in the serum and BALF, and no significant correlation was observed between the concentrations of these carbohydrate antigens in BALF and clinical findings. Immunohistochemical study of SLX and CA19-9 in open lung biopsy specimens obtained from patients with DPB showed expression of SLX and CA19-9 on the bronchiolar surface epithelial cells and mucinous exudates in air spances. These results indicate that carbohydrate antigens are presumably increased in the pulmonary lesions of patients with DPB, and this increase causes high levels of these antigens in the serum. Furthermore, we investigated the change of concentrations of SLX and CA19-9 in BALF obtained from patients with DPB after erythromycin (EM) treatment. The concentrations of these two antigens were decreased after EM treatment.


[Pulmonary function and exercise tolerance in patients treated with bone marrow transplantation (BMT)].

We assessed pulmonary function and exercise tolerance in 10 BMT patients. Their underlying disorders were as follows; chronic myeloid leukemia 5 cases, acute lymphoblastic leukemia 2 cases, aplastic anemia, acute myeloid leukemia and non-Hodgkin's lymphoma one case each. Their mean age was 26 +/- 9 years old. When the patients were healthy and free of serious complications and anemia, arterial blood gas examination, pulmonary function tests and incremental treadmill exercise test were examined repeatedly. Although %VC and FEV1.0% kept within normal range, PaO2 at rest, %DLCO, VO2max, VO2max/kg and O2-pulsemax remained low at one year after BMT. There were significant correlations between VO2max and O2-pulsemax [r = 0.955 (p < 0.001)], %VC [r = 0.758 (p < 0.02)], VE/VO2max [r = -0.749 (p < 0.02)] and delta SaO2/VO2/kg [r = -0.731 (p < 0.02)], suggesting that exercise intolerance in BMT patients may be based on both cardiac and gas exchange abnormalities. To evaluate cardiac dysfunction, we compared exercise parameters obtained at an exercise level of 75% predicted heart rate max in five age-matched normal subjects to those in six BMT patients who did not demonstrate desaturation during exercise. As a result, the mean values of VO2max/kg and O2-pulse/m2 in BMT patients were significantly lower than those in normal subjects, suggesting that cardiac dysfunction may be due to insufficiency of stroke volume during exercise. It is concluded that exercise intolerance in BMT patients may be mainly due to cardiac dysfunction.


[Serum 7S collagen levels in diffuse interstitial lung diseases--an index of the destruction of alveolar structure].

To examine whether alteration of 7S collagen in the alveolar basement membrane is related to the condition and prognosis of diffuse interstitial lung diseases (idiopathic interstitial pneumonia: IIP, collagen vascular diseases, sarcoidosis, and hypersensitivity pneumonitis), we measured serum 7S collagen levels in 123 patients with diffuse interstitial lung disease and other lung diseases. Patients with diffuse lung diseases (diffuse interstitial lung disease, pulmonary emphysema, and diffuse panbronchiolitis: DPB) showed significantly higher serum levels of 7S collagen than healthy normal controls. Serum 7S collagen levels in IIP and collagen vascular diseases were significantly higher than those in pulmonary emphysema and DPB. In cases of IIP, serum 7S collagen levels in the active stage were significantly higher than those in the inactive stage. Furthermore, the prognosis of patients with higher serum 7S collagen levels was significantly poorer than those of patients with lower serum 7S collagen levels. In infectious pulmonary diseases, serum 7S collagen levels of patients with adult respiratory distress syndrome (ARDS) were significantly higher than those of patients without ARDS. Autopsy specimens obtained from patients with positive serum 7S collagen showed diffuse alveolar damage and/or diffuse pulmonary hemorrhage in the alveolar areas. Immunohistochemical staining for 7S collagen showed disruption and/or loss of the alveolar basement membrane. The authors conclude that serum level of 7S collagen is useful for estimating the activity of diffuse interstitial lung diseases as an index of the destruction of alveolar structure.


[Alteration of oxygen extraction and blood flow in various organs under acute hypoxia].

To assess the compensatory mechanisms involved in maintaining aerobic metabolism in various organs during exposure to acute hypoxia, five anesthetized and paralyzed dogs were ventilated with either normoxic (FIO2: 0.21) or hypoxic gas mixture (FIO2: 0.13). Under both conditions, we examined systemic and pulmonary hemodynamic parameters, and took samples of arterial and mixed venous blood as well as venous blood from various organs including the heart, brain splanchic organs (hepatic vein) and kidney. Based on PO2, PCO2 and pH values as measured with electrodes, we calculated O2 and CO2 contents in each blood sample. The values thus obtained were then used to estimate the O2 extraction ratio (ER), gas exchange ratio (R) and difference of base excess between arterial and venous blood (avBE) in the whole body as well as in each organ. In addition, both O2 delivery (DO2) and O2 consumption (VO2) in the whole body were calculated. Although the whole body showed a decrease in DO2 and an increase in ER during hypoxic gas breathing, other parameters including R, avBE and VO2 did not change significantly. Higher ER values were found in the heart and brain than those in the splanchic organs and kidney, the qualitative trend being the same irrespective of FIO2. On the other hand, increase in ER during hypoxic gas breathing was considerably larger in the splanchic organs and kidney than that in the heart and brain. There was no significant difference in R and avBE in any of the organs between normoxic and hypoxic conditions.(ABSTRACT TRUNCATED AT 250 WORDS)


[Clinical study on benefit and safety of frequent inhalation of aerosolized procaterol hydrochloride in aged acute asthmatics].

We studied the hemodynamic effects of frequent inhalation of aerosolized procaterol hydrochloride (PRC) in the treatment of status asthmaticus. Twenty patients were enrolled and divided into 2 groups; younger group (less than 55 years; n = 11) and older group (more than 55 years; n = 9). All patients were treated with intravenous hydrocortisone (4 mg/kg/4 h) and PRC inhalation (30 micrograms; 0.3 ml) every hour via a jet nebulizer with 3 l/min oxygen for four consecutive days. Holter ECG monitoring was performed on the 1st, 4th, and 7th days of hospitalization to evaluate mean heart rate, tachycardiac incidence, and arrhythmias. Blood pressure, serum potassium levels, and peak expiratory flow rate (PEFR) were measured on the same day. Even though the total dosage of inhaled PRC on the 1st day was 496.4 +/- 62.61 micrograms for the younger group and 490.0 +/- 36.73 micrograms for the older group (p = NS), total arrhythmic ratios were less than 1% in both group. Both blood pressure and heart rate decreased with improvement of symptoms and PEFR value. Serum potassium levels tended to decline according to the administered dosage of PRC (p < 0.01); however, severe hypokalemia less than 3.0 mmol/l was not observed. We conclude that frequent inhalation of PRC (up to 500 micrograms/day) via a jet nebulizer provides rapid relief from acute asthmatic attacks, and is safe clinically even in aged asthmatics receiving intravenous steroids.


[A case of Legionella pneumonia with myelodysplastic syndrome].

A 40-year-old man was admitted with high fever and cough. Pneumonic shadows of the left middle and lower lung fields increased rapidly, and his blood gases worsened. Initial treatment with cefmenoxime, piperacillin, and minocycline was ineffective. Administration of rifampicin was started for suspected legionella pneumonia, but it did not control the spread of the pneumonia shadows. After addition of an antifungal agent and trimethoprim-sulfamethoxazole, his symptoms gradually improved. Isolation of Legionella pneumophila from sputum specimens collected on the 4th day of admission confirmed the diagnosis on day 10. The patient was then given oral rifampicin plus cefmenoxime to prevent mixed infection, and showed a satisfactory improvement. Legionella pneumonia developed secondary to compromise of the patient's immunity due to steroid therapy for MDS. After recovering from Legionella pneumonia, the patient subsequently developed tuberculous pleurisy and Pneumocystis carinii pneumonia, which were cured by antituberculous therapy and trimethoprim-sulfamethoxazole. However, acute hepatitis followed by hepatic failure developed, and he died on day 121 after admission.


[Theophylline toxicity in a patient with status asthmaticus].

A 70-year-old woman was hospitalized for status asthmaticus. The level of CRP was high and chest roentgenogram showed infiltrative shadows in the left middle lung field. Artificial respiration and continuous infusion of methylprednisolone and aminophylline 750 mg/24 hr were performed. Eight hours after admission, seizures suddenly occurred. At this time, brain CT showed no abnormal findings. The seizures were thought to be induced by theophylline toxicity, since serum theophylline concentration was high at 69.9 micrograms/ml. Because theophylline clearance of the patient in a clinically stable condition was normal, it was speculated that theophylline clearance was reduced during status asthmaticus. It is thought that this rare case of theophylline toxicity occurred due to reduction of theophylline clearance during status asthmaticus associated with pneumonia.


[A case of allergic bronchopulmonary aspergillosis with no history of bronchial asthma].

A 53-year-old male was admitted to our hospital because of an abnormal shadow in the left upper lung. Bronchofiberscopy revealed edematous mucosa and pus at the orifice of the left upper lobe bronchus. Pathological examination revealed bronchial inflammatory change with infiltration of eosinophils and also the existence of aspergillus in the pus. Mild eosinophilia and elevation of serum IgE level were observed in the peripheral blood, and serum precipitin against Aspergillus fumigatus was positive. Bronchogram showed central bronchiectasis, and the diagnosis of allergic bronchopulmonary aspergillosis (ABPA) was made. In cases of ABPA, bronchial asthma is usually present prior to presentation, but this patient had no history of asthma even though airway hyperresponsiveness to methacholine was confirmed.


[Three cases of chronic respiratory tract lesions associated with adult T-cell leukemia (ATL)].

Three cases of chronic respiratory tract lesions as a complication of adult T-cell leukemia (ATL) are reported. Case 1 was seropositive for HTLV-1 on recent examination following treatment of bronchiolitis. Chest radiograph revealed over inflation of the lungs and bilateral diffuse small nodular shadows. Pulmonary function test resulted hypoxemia and mixed ventilation disorder. Pathological examination confirmed lymphocytic infiltration of the bronchiolar wall. Both clinically and pathologically the patient was diagnosed as having diffuse panbronchiolitis (DPB). Therefore, this case was considered to be the bronchiolar type of HTLV-1 associated bronchiolo-alveolar disorder (HABA). The other two cases with smoldering or chronic ATL presented with long-standing symptoms of productive cough due to chronic respiratory lesions. We consider that all three cases had HTLV-1 virus associated pulmonary lesions, but with different clinical and pathological presentations. Among 12 cases of bronchiolitis experienced at our hospital, three were positive for HTLV-1.


[A case of idiopathic pulmonary fibrosis with histology of usual interstitial pneumonia that responded to pulse therapy followed by combined immunosuppression with prednisolone and azathioprine].

A 64-year-old woman who was admitted with cough and dyspnea showed severe hypoxemia and interstitial lung shadows. The clinical diagnosis was idiopathic interstitial pneumonia (synonymous with idiopathic pulmonary fibrosis in the United States), since there were no specific immunological or bacteriological findings. No clinical signs or laboratory data compatible with collagen disease were observed. Methylprednisolone pulse therapy was given followed by prednisolone (0.8 mg/kg) and azathioprine (15 mg/kg). Marked improvement of hypoxia, chest X-ray and spirometry results was observed after five weeks. Histological examination of an cases of residual interstitial shadow obtained by open lung biopsy revealed usual interstitial pneumonia. Tapering of the immunosuppressant drugs led to a recurrence 3 months later, which was controlled by reintroduction of the same regimen. Therefore, only prednisolone was tapered, and data obtained in an outpatient clinic 6 months after the recurrence were as follows: %VC 108%, %DLco 72%, PaO2 80 Torr. The value of this regimen for acute IPF or exacerbation of IPF is suggested because of its life-saving effects.


[A case of cardiac sarcoidosis associated with various clinical symptoms and thrombocytopenia].

A 29-year-old man presented with acute onset of high fever, chest pain and dyspnea. Chest X-ray film showed diffuse interstitial shadows, a cavitary lesion in the left upper lung field and cardiomegaly, but no lymphadenopathy. Abdominal CT scan showed hepatosplenomegaly and multiple small low density areas in the liver and spleen. Electrocardiogram demonstrated multifocal ventricular premature beats and ventricular tachycardia. Cardiac catheterization revealed left ventricular aneurysms. Sarcoidosis was confirmed by lung and liver biopsy. Drug therapy of prednisolone and mexiletine resulted in clinical improvement of symptoms, signs and chest X-ray film, but platelet count decreased gradually. It is suggested that an immune mechanism of sarcoidosis may have been the cause of this thrombocytopenia.


[A case of primary alveolar hypoventilation syndrome with a good response to nocturnal low-flow oxygen inhalation and negative pressure ventilation].

A 34-year-old female was admitted on June 25, 1990, for the evaluation of alveolar hypoventilation which worsened after her second delivery. She showed impairment of both hypercapnic and hypoxic ventilatory responses, and marked desaturation due to hypopnea and apnea during sleep. Although administration of methylxanthine and medroxyprogesterone was not very effective, after treatment with low flow oxygen, there was a marked decrease in the frequency and duration of desaturation during sleep and improvement of arterial daytime blood gases, which suggested the existence of hypoxic ventilatory depression in the pathophysiology of her nocturnal desaturation. Furthermore, the use of a negative pressure ventilator for 3 hours in the daytime for 10 days resulted in marked improvement of symptoms, arterial blood gases, respiratory muscle strength, and the frequency and duration of sleep desaturation. These findings suggest that both low flow oxygen therapy during sleep, and daytime negative pressure ventilation may be beneficial in patients with primary alveolar hypoventilation and central sleep apnea syndrome.


[A case of endobronchial minute leiomyoma and literature review of the 66 cases of endotracheal and endobronchial leiomyoma reported in Japan].

A case of endobronchial minute leiomyoma successfully treated by bronchoscopically directed forceps biopsy is described. A 42-year-old male with a 20 pack-year smoking history was admitted for dry cough occurring at night. Chest X-ray showed no abnormal shadows. The tumor, measuring 2 by 2 mm, was located in the right B7. The clinical characteristics of the 66 cases of endotracheal and endobronchial leiomyoma reported in Japan are also discussed. The male to female ratio of this disease was 2:3. Middle-aged people were most, commonly affected. Usually, obstructive pneumonia or atelectasis, which develops distal to the lesion, causes respiratory symptoms and chest X-ray abnormality. However, 10% of cases were asymptomatic and 30% had a negative chest X-ray. There were 7 cases of endobronchial minute leiomyoma, measuring less than 10 mm in diameter. Of these, three cases had only hemoptysis and had no chest X-ray abnormality. In such cases fiberoptic bronchoscopy is may be the only useful procedure for the diagnosis of this disease.


[A case of eosinophilic pneumonia with diffuse reticular shadows and scattered nodular shadows on chest X-ray film--comparison of findings of chest X-ray and lung histology].

A 47-year-old woman was admitted to our hospital because of dry cough and throat discomfort. Chest X-ray film showed reticular shadows with Kerley B line and scattered nodular shadows. Blood examination revealed normal WBC count (5100/mm3) with eosinophilia (21%), negative CRP, elevated ESR (49 mm/l hr), normal IgE level and positive antinuclear antibody with speckled pattern. Skin tests and precipitating antibodies for common allergens were negative. Results of arterial blood gas analysis and respiratory function test were almost normal. Bronchoalveolar lavage fluid yields 85.7% eosinophils, which suggested eosinophilic lung disease. To establish the diagnosis, thoracotomy was performed and lung specimens were obtained from S3a and S8a. In the area of the nodule, the alveolar spaces were filled with eosinophils and mononuclear cells, with no evidence of vasculitis, granuloma or parasites. Alveolar spaces were almost preserved in residual areas. The walls of air ways, pleura and lobular septa were heavily infiltrated with eosinophils and mononuclear cells. Thus, open lung biopsy confirmed the diagnosis of idiopathic eosinophilic pneumonia. The areas of intraalveolar filling with eosinophils and mononuclear cells were found to correspond to the nodular shadows on chest X-ray film. The relationship between the findings of chest X-ray films and lung histology are discussed.


[Two cases of familial pulmonary arteriovenous fistula].

Two cases of familial pulmonary arteriovenous fistula are reported. Case 1: A 54-year-old woman was admitted with exertional dyspnea. An abnormal shadow on chest X-ray had been noted since the age of 37 years. Pulmonary angiography demonstrated bilateral pulmonary arteriovenous fistulas. Case 2: A 25-year-old man, the son of Case 1, was admitted for operation for the same disease. The mother and son both suffered from repeated epistaxis due to Rendu-Osler-Weber disease. In order to reserve pulmonary function, fistulectomy was performed in both cases, and their subsequent clinical courses were good.


[Child psychotherapy in medical practice and the clinic--15 years of the "Brühl Model"].

Living in an industrial society places considerable stress on children and on adolescents, to which they react with behavioural disturbances and psychosomatic disorders. So far, physicians have been trained only insufficiently at universities with regard to psychotherapy, which means they cannot cope sufficiently with such problems if they are confronted with them in their clinical and practical work. Hence, a continuing education programme called the "Brühl Model" has been worked out which imparts knowledge on child psychology and child psychotherapy by means of three-year courses based on depth psychology. This corresponds to the "small-scale psychotherapy in medical practice" as conceived by J. H. Schultz and M. Balint. This educational programme has been largely adapted to the demands made at the Manheim Physicians' Congress in 1977 with regard to acquiring adequate proficiency in the subject of psychotherapy, and has been accepted by the German professional boards of physicians. 600 colleagues have since been undergoing this training during the past 15 years with success. The present seventh training course is now also open to the colleagues from the new German Laender of the former GDR.


[Clinical importance of Helicobacter pylori infections in childhood].

Within the last ten years an increasing number of Helicobacter pylori-related inflammatory gastroduodenal diseases in children has been reported. The aim of this paper is to describe the range of Helicobacter pylori infections in children including diagnosis and treatment by application of colloidal bismuth salts.


[Vaccination--duty and voluntary consent].

High mass inoculation rates--e.g. against measles, mumps and rubella or German measles--are mandatory in highly industrialised countries to keep circulation of wild strains of viruses as low as possible. In the GDR this was achieved, inter alia, by compulsory vaccination. Although compulsory vaccination is possible in the FRG as well, in accordance with the Federal Epidemics law, it needs a special ordinance requiring to be approved by the Federal Council. This, in turn, will be forthcoming only if there is an incidence of infectious diseases occurring in a malignant form of if it is to be expected that they will be spreading in the manner of an epidemic. Experiences gathered in other European countries (France, Italy) and in the U.S.A. have shown that success of compulsory vaccination depends on early control. Examples in individual Federal Laender and in England prove that high mass inoculation rates can be achieved even without compulsion if there is close cooperation between practising paediatricians and Public Health services.


[School performance of former premature infants in the first four years of school].

School achievement during the first four grades was analysed by means of subject marks in 203 prematurely born and in 140 maturely born children. In subjects referring to behaviour in the classroom, no statistically significant differences in average marks could be found between prematurely born children and the control group. The average marks in performance subjects were slightly higher in the subgroup of very prematurely born children. However, statistically significant lower marks were observed in the subject of sports only, and for formerly immature children also in the subject of manual training. The higher the educational level of the mothers, the better the average marks without sports. No relationships between school performance and manifestation of postnatal risk factor like Apgar score, blood gas values and duration of oxygen dependency could be seen. These results demonstrate that school performance of former premature infants lies within the normal variance of their grade.


[Rate of intrauterine growth retardation at the Leipzig Perinatal Center comparing the years 1982 to 1984 with 1987 to 1989].

Referring to the number of all live-born children, hypotrophic newborn (IUGR) were classified at the Centre for Perinatal Care in Leipzig into two periods of time. Based on the 5th Kyank-percentile 6.5% hypotrophic newborn were classified into period A (1982-1984) and 5.0% hypotrophic newborn were classified in period B (1987-1989). The proportion of hypotrophic newborn with a birth weight < 2500 g amounted to one quarter of all infants (except multiple birth) with low birth weight in period A and to one fifth (20.7%) in period B. The decrease in the rate of hypotrophy in these infants affected nearly exclusively the mature ones. The number of infants with extreme intra-uterine growth retardation amounted to 29% (99 in 329) in period A and to 24% (58 in 238) in period B. The rate of hypotrophy in stillbirths decreased from 44% to 33%. In this process the proportion of extremely hypotrophic stillbirths amounted to 47% in period A, whereas it decreased to only 26% in period B.


[Pneumococcal cellulitis].

Streptococcus pneumoniae as a cause of cellulitis is rarely reported in children and adults. We report on an infant with facial cellulitis due to pneumococci and review already described cases since 1975. The main features of this infection, underlying diseases and problems of diagnostics and therapy are discussed.


[Mendelson syndrome in childhood].

Mendelson's syndrome is characterized by bronchoconstriction, intraalveolary pulmonary oedema and insufficiency of the right heart. We report an unusual case of Mendelson's syndrome in infancy. The morphological findings, combined with the discussion of the pathophysiological stages, are presented.


[Arteriovenous fistula of the blood vessels of the neck--a rare differential diagnosis of venous hum in childhood].

In a case report it is shown that in rare circumstances there might be an extracardial organic cause for heart murmurs sounding accidentally. In a child with the finding of a venous hum an arterio-venous fistula between the right common carotid artery and the right internal jugular vein could be demonstrated by colour-coded echocardiography. The clinical relevance of this finding is discussed.


[Physician graduate and continuing education from the viewpoint of new legal requirements].

Continuing and specialist education are inseparably linked to professional activities. The changes and especially the new legal aspects that have arisen since the GDR joined the FRG, are described.


Project lifestyle: developing positive health lifestyles for schoolchildren in Antigua.

Countries of the English-speaking Caribbean are in epidemiological transition. Following 30 years of socioeconomic change, obesity and chronic diseases have almost replaced malnutrition and infectious diseases as major health problems. Major risk factors for this modern epidemic are lifestyle-related. Project Lifestyle seeks to develop positive health lifestyles in schoolchildren gradually, sequentially, and systematically from grades 1-12 and throughout the school system on the island of Antigua. The four health habits addressed include weighing right, eating right, doing daily physical exercise, and having a positive self-concept. Since risk interventions with schoolchildren have produced positive results in several developed countries, this project developed an intervention methodology in the Caribbean context.


Patterns of alcohol and other drug use in an Iowa community.

From a baseline survey of high school students in two school systems, information was obtained to describe patterns of alcohol and other drug (AOD) use and adverse consequences of use, compare indices of AOD use and consequences for grade level and gender differences, and examine relationships of indices to selected individual, family-related, and social competence/adjustment-related risk factors. Though use of illicit drugs was reported at low levels, prevalence of drinking and incidence of binge drinking were relatively high. Increases in AOD use and adverse consequences with age and grade level were found, but gender differences were not found. Relationships of AOD use and adverse consequences to selected individual, family, and social risk factors were consistent with a substantial body of prior work but exceptions were found. Strongest correlations to both indices were found for risk taking, sense of mastery, family management/cohesion, peer pressure, and social/school adjustment.


Sources of stress in children with asthma.

Children experience stressors related to self-concept and school, family, and peer relationships. This study of children with asthma determined their perceptions of the frequency and severity of stressors they experience other than their asthma. Children with asthma are similar to peers with regard to perceptions of stressors. Teachers, health professionals, and parents should consider children with asthma as normal children who have an additional source of stress--a chronic illness. Results suggest perceptions of most stressors relate more strongly to gender-role development than to asthma. Children with asthma rated feeling left out of the group and not being good enough at sports as serious stressors. School personnel could be instrumental in encouraging management and prevention of exercise-induced asthma and promote all children's full participation in physical activities. Further examination of the relationship between stress and asthma is needed.


Using the PRECEDE model to determine junior high school students' knowledge, attitudes, and beliefs about AIDS.

The effectiveness of a one-period school-based AIDS education program on an adolescent population of seventh and eighth grade students (N = 585) was determined. An instrument based on the PRECEDE model was used to assess program effectiveness. Three-way analysis of variance indicated significant differences (p v .01) between pretest to posttest scores for knowledge, attitude, and beliefs for those who received the program versus those who did not by grade and gender of students. The intervention group scored significantly higher than the comparison group on knowledge gain for both seventh and eighth grade students and for males and females. On attitude items, a significant increase occurred from pretest to posttest for eighth grade students who received the program, but not for seventh grade students. The experimental group of eighth grade students scored higher on the attitudes component than the comparison of eighth grade students on the posttest. When attitudes were examined by gender for females in the educational intervention, an increase occurred in attitude scores from pretest to posttest. While belief scores increased significantly from pretest to posttest for the experimental seventh and eighth grade students, significant increases occurred only for experimental group females. Findings support the contention that a one-class period AIDS education program can affect more than just knowledge since attitudes and beliefs also were partially affected.


Drug use and anticipated parental reaction among rural school pupils in Zimbabwe.

Study participants included 285 secondary school pupils in Zimbabwe who responded to a questionnaire assessing alcohol, tobacco, and marijuana use, and anticipated parental reaction to the pupil's drug-taking behavior. Results showed nearly 17% of the sample had used alcohol, 8% used tobacco, and 5% had used marijuana during the past seven days prior to questionnaire administration. Results regarding intentions to use alcohol, tobacco, and marijuana in the future show pupils' interest highest in using alcohol. Nearly 34% indicated intentions to use alcohol during the next year, while 16% reported intentions to use tobacco, and 12.9% indicated intentions to use marijuana. Nearly 17% reported they felt their parents would be favorable to their use of alcohol. Anticipated parental approval for tobacco and marijuana was 13.6% and 10.8%, respectively. Though current use and future intentions among the sample are not as high compared to similar populations in developed countries, this study suggests Zimbabwe should consider expanding its drug education effort in the school setting. Research to identify effective educational strategies to curb further increases in adolescent drug taking behavior also needs to be explored and identified.


Introductory remarks: development of chemopreventive agents for prostate cancer.

The term "cancer chemoprevention" refers to the prevention of cancer by intervening with drugs prior to the malignant (i.e., invasive) stage of carcinogenesis. The development of chemopreventive drugs is the major objective of the Chemoprevention Branch at the National Cancer Institute. The testing of drugs for cancer chemoprevention differs from testing of those for cancer treatment. Chemopreventive drug trials involve healthy target populations, and the endpoints of reduced cancer incidence or mortality, reduced/eliminated precancerous lesions, or increased latency must be achieved with little or no drug toxicity. The design of cancer chemoprevention trials for prostate presents several problems, such as the age of the study population and undependable methods for detecting microscopic foci by sequential sampling. A major motivation for organizing this workshop is the development of strategies for the design of chemopreventive intervention trials for prostate cancer. One of the most difficult problems of chemoprevention drug testing is the necessity of lengthy trials due to the long developmental period of many cancers. This is especially true for prostate cancer. A major solution to the problem is the use of intermediate biomarkers, defined as morphological or molecular intraepithelial changes that can constitute short-term endpoints in chemoprevention clinical trials. They are categorized as histological, genetic, proliferation-related, and differentiation-related. Modulation of intermediate biomarkers, instead of cancer incidence, as trial endpoints would allow chemoprevention trials to be of shorter duration, to use fewer subjects, and to be of lower cost. Review of the current status of prostatic intermediate biomarkers, and methods for identifying and validating them, are also major reasons for convening this workshop.


Prostatic intraepithelial neoplasia (PIN): current concepts.

Prostatic intraepithelial neoplasia (PIN) represents the putative precancerous end of the morphologic continuum of cellular proliferations within prostatic ducts, ductules and acini. Two grades of PIN are identified (low grade and high grade), and high grade PIN is considered to be a precursor to invasive carcinoma. The continuum which culminates in high grade PIN and early invasive cancer is characterized by basal cell layer disruption, basement membrane disruption, progressive loss of secretory differentiation markers, increasing nuclear and nucleolar abnormalities, increasing proliferative potential, and increasing variation in DNA content (aneuploidy). Clinical studies suggest that PIN predates carcinoma by ten years or more, with low grade PIN first emerging in men in the third decade of life. The clinical importance of recognizing PIN is based on its strong association with carcinoma; its identification in biopsy specimens of the prostate warrants further search for concurrent invasive carcinoma.


Neoadjuvant hormonal manipulation: a strategy for chemoprevention trials.

Androgen ablation using hormonal manipulation is used extensively in metastatic prostate cancer; however, its use in localized disease combined with surgical extirpation of the gland has not been thoroughly and systematically investigated. The rationale for neoadjuvant therapy stems from the demonstrated effectiveness of androgen ablative therapy in metastatic disease and the high rate of "positive" surgical margins, especially in patients with Stage B2 disease. In addition, the essentially anecdotal clinical report of Scott and Boyd [1], using endocrine therapy plus radical prostatectomy in patients with Stage C disease, gives 15 year survival results comparable to those obtained by Jewett [2] in Stage 1 patients treated by radical prostatectomy. Finally, experimental observations in the androgen-sensitive mammary tumor (Shionogi) lend support to the concept of neoadjuvant hormonal manipulation. A pilot study of neoadjuvant endocrine therapy in 55 patients treated at Memorial Sloan-Kettering Cancer Center with 3 months of diethylstilbestrol (DES) (3 mg/day) prior to radical prostatectomy indicates marked reductions in prostate-specific antigen (PSA), although persistent evidence of adverse local tumor features was common. Some patients, however, exhibited evidence of significant downstaging. Whether or not any alteration in disease progression will accrue from demonstrated local downstaging is, of course, uncertain. However, clinical and laboratory effects of such treatment may provide a means for correlation with subsequent tumor behavior, and may prove useful in treatment decisions. Additionally, a decrease in the number of foci of grade 3 prostatic intraepithelial neoplasia (PIN-3) was noted in a small number of patients.(ABSTRACT TRUNCATED AT 250 WORDS)


Chemoprevention in prostate cancer: the role of difluoromethylornithine (DFMO).

The polyamines are normal cell constituents considered to have an important role in the regulation of proliferation and differentiation. DFMO is an irreversible, enzyme-activated, suicide inhibitor of ornithine decarboxylase (ODC), the enzyme responsible for the first and rate-limiting step in mammalian polyamine synthesis. Preliminary data show that DFMO inhibits tumor cell growth in vitro and in vivo, and that it demonstrates chemopreventive activity in a variety of animal tumors. The prostate contains some of the highest concentrations of polyamines and of polyamine-synthetic enzymes (including ODC) in the mammalian organism. ODC activity in the prostate was shown to be more susceptible to DFMO inhibition than in other organs. We have found the ODC activity of the Dunning R3327 rat prostatic carcinomas to be as sensitive to inhibition by DFMO as the normal rat prostate. Furthermore, DFMO was inhibitory to the growth of the tumor both in vitro and in vivo. Given the slow growth rate and long latency period of human prostate cancer and the preliminary DFMO data, we suggest that clinical trials to evaluate the chemopreventive potential of DFMO in prostatic carcinoma deserve serious consideration.


When is intervention warranted?

A chemoprevention trial in prostate cancer would be a formidable but potentially rewarding study. The current status of knowledge of drug interactions with, biomarkers of, and even the natural history of prostate cancer is insufficient to study all levels of men at risk. Currently, the most promising group to study is group I--those men with a high probability of developing prostate cancer but who do not currently have evidence of the disease. This could be a placebo-controlled, prospective and randomized study with the endpoint being clinically-detected prostate cancer. In addition, much may be gained from short-term pilot studies of "chemo-active" agents on morphologic and other biomarkers of prostate cancer initiated immediately before surgical removal. It is hoped that such studies may provide rationale for future efforts directed at preventing progression of premalignant or early prostate cancer lesions.


The natural history of adenocarcinoma of the prostate.

All analyses of the efficacy of therapy for prostate cancer must control for the natural history of the disease. Over the past years, several long-term series involving several hundred patients have helped to describe the results of untreated disease. In general, most patients will not die of their disease, although approximately half of the patients will develop disease progression within 10 years. Predictors of progression include tumor stage, grade, and ploidy status.


New relationships between prostatic intraepithelial neoplasia and prostatic carcinoma.

Our group has been studying the progressive molecular changes in prostatic epithelium which precede the invasive phenotype. Initial studies revealed similar alterations in cytoskeletal proteins between high grade prostatic intraepithelial neoplasia (PIN) lesions and invasive carcinoma. Specifically we observed an increased expression of certain cytokeratins and decreased expression of vimentin. We also noted a change in glycosylation as detected by Ulex europaeus staining. Using the latter technique we were able to microdissect and isolate nuclei from areas of low and high grade PIN lesions as well as from invasive carcinoma for morphometric analysis. Similarities in nuclear size, chromatin heterogeneity, and nuclear DNA content between low and high grade PIN and invasive carcinoma in carcinomatous specimens were noted. In contrast, these parameters were significantly different in low grade PIN lesions obtained from benign prostatic transurethral resection (TURP) specimens. In addition, DNA histograms revealed similar proliferative indices between high grade PIN and invasive carcinoma, which differed significantly from low grade PIN. Parameters thought to be relative to the invasive phenotype were also examined, such as the members of the metalloproteinase family; although normal luminal cells fail to express detectable levels of these enzymes, invasive carcinoma and even low grade PIN lesions express both the 72 kDa and 92 kDa type IV collagenase. Taken together, these data indicate that the dysplastic cells of PIN lesions and carcinomas are similar in nuclear and genomic features as well as protease expression. Our current working hypothesis is that these cells are already armed with the necessary proteases to invade the basal lamina but in an inactive form. Tumor progression requires an additional event of protease activation.


DNA ploidy: early malignant lesions.

The nuclear DNA content of prostate cancer specimens, both needle biopsies and aspiration biopsy specimens as well as transurethral resection (TUR) chips and radical prostatectomy specimens, can now be reliably measured by standardized methods of flow and static image cytometry. For prostate carcinomas of every clinical stage (A1-D2), DNA diploid tumors have a better prognosis than tumors of a similar stage and grade which are non-diploid. Of particular importance to this symposium is the fact that DNA diploid stage D1 and D2 tumors treated early by androgen deprivation generally have a remarkably good prognosis. In contrast, those patients with DNA non-diploid tumors progress early despite androgen deprivation. Such a result suggests that DNA ploidy can be used to identify prostate cancers which are potentially sensitive to hormonal manipulation. Additional investigations from several groups indicate that early stage prostate malignant lesions, for example stages A1, A2, B1, and B2, are generally DNA diploid (about 75%). Swedish data suggest a steady progression of prostate cancer from early diploid to tetraploid, to non-tetraploid aneuploid, to multiple stemline aneuploid tumors with time and advancing stage. Taken together, these data suggest that the earliest detectable prostate carcinomas should be overwhelmingly DNA diploid. A large majority of these patients with early tumors should be candidates for "chemoprevention" by pharmacologic methods which reduce the effective androgen stimulation of prostate tumor cells.


Aneuploidy and nuclear features of prostatic intraepithelial neoplasia (PIN).

Quantitative analyses (QAs) of prostatic intraepithelial neoplasia (PIN) helped to objectively define some traditional features of the lesion because, first, changes in value are represented by numbers and not by subjective evaluation of morphologic clues. QAs have also helped to identify subtle abnormalities. For example, the degree of nucleolar margination is a new diagnostic feature which can be easily evaluated as the proportion of nucleoli touching the nuclear membrane. Thirdly, QAs have provided useful insights into understanding some morphologic changes. PIN, in fact, appears to be characterized by complex changes which involve the secretory cells as well as the basal layer and which affect the surrounding stroma. In the epithelial lining, two types of simultaneous changes take place, the first in the nucleus (expression of abnormal proliferative and/or renewal activity) and the second in the cytoplasm (expression of the disorder in cell differentiation), pointing out that only PIN samples of high grade can be considered as having acquired the characteristics of a neoplastic lesion.


Transforming growth factor beta 1 as a biomarker for prostate cancer.

Using the mouse prostate reconstitution (MPR) model system, under conditions where the ras and myc oncogenes are introduced via a recombinant retrovirus into both the mesenchymal and epithelial compartments of the urogenital sinus, poorly differentiated prostate cancer is produced with high frequency (> 90%) using inbred C57BL/6 mice. Northern blotting and immunohistochemical analysis showed that the transition from benign prostatic hyperplasia (BPH) to prostate cancer is invariably associated with the induction of elevated transforming growth factor-beta 1 (TGF-beta 1) expression. Similar analysis of TGF-beta 1 in human BPH and prostate cancer is consistent with our MPR results and indicates that the accumulation of extracellular TGF-beta 1 is significantly more intense in prostate cancer compared to normal or benign prostate tissues. Interestingly, where benign pathologies are observed in the prostatic stroma in the presence of benign prostatic epithelium, extracellular TGF-beta 1 is seen predominantly in the stromal compartment. Experimental studies clearly demonstrate that mRNA levels of TGF-beta 1 and other growth related genes are regulated by androgens in prostate cancer cells. Overall, our results suggest that elevated TGF-beta 1 is involved in the development of prostate cancer. Direct determination of TGF-beta 1 levels and distribution as well as analysis of localized and systemic effects produced by TGF-beta 1 may serve as useful biomarkers for prostate cancer.


Prostate cancer tumor location as predicted by digital rectal examination transferred to ultrasound and ultrasound-guided prostate needle biopsy.

The advent of transrectal ultrasound (TRUS) and the Biopty instrument (Bard Urologic) has revolutionized prostate biopsy (PNB). Theoretically the systematic multiple biopsy approach offers the advantage of less sampling error with respect to presence of carcinoma, grade of carcinoma and sites of tumor within the gland. These parameters may be important in selecting the therapeutic approach and, if radical prostatectomy is contemplated, in modifying the operation as indicated based on tumor location. In the present investigation, we received specimens obtained from 100 men with clinically localized prostatic carcinoma who had previously undergone ultrasound-guided systematic random biopsy (TRUSPNB) along with TRUS and digital rectal exam (DRE). Among the 372 sectors with carcinoma identified in the 100 radical prostatectomy specimens, significant underrepresentation by TRUSPNB was noted (39% false negative). When an abnormality on either DRE, TRUS or TRUSPNB was observed, the sensitivity was 65%. The specificity was 89% when all three tests were abnormal. It would appear that preoperative assessment of tumor location is inadequate with the current modalities available. There may, however, be subsets of patients which would benefit by tumor location utilizing DRE, TRUS and TRUSPNB.


Cancer detected incidental to simple prostatectomy (stage A1).

The incidence of stage A (incidental) adenocarcinoma of the prostate in transurethral resection (TUR) specimens is approximately 16%. This paper discusses the criteria for differentiating stage A1 versus stage A2 tumor, based on tumor volume and grade. Both the short-term (4 year) and long-term (8-10 year) natural history of untreated stage A1 prostate cancer are examined. Options to follow patients expectantly are presented. These include digital rectal examination and transrectal ultrasound. Specific problems relating to analyzing transrectal ultrasounds in patients who have had a prior TUR are addressed. Also, the unique aspects of transrectal ultrasound for stage A1 disease as it relates to the location of the lesion are expanded upon. The third option in the management of stage A1 disease is to monitor serum prostate specific antigen (PSA) levels. Areas covered include the sensitivity and specificity of PSA in general, and, in specific, serum PSA levels following TUR for stage A1 disease as a predictor of residual tumor. New data on a small group of patients who underwent delayed radical prostatectomy following diagnosis of stage A1 disease, where PSA data was available, are presented. The rationale for following patients with stage A1 disease by monitoring their serum PSA levels is supported by data from a group of men with normally sized prostates, benign prostatic hyperplasia, or cancer where longitudinal serum PSA levels were available. Finally, the option of radical prostatectomy for stage A1 disease is put forth. Data include a study of a large group of radical prostatectomy specimens performed for stage A1 disease.(ABSTRACT TRUNCATED AT 250 WORDS)


The Lobund-Wistar rat model of prostate cancer.

Two models of preventable metastasizing autochthonous prostate adenocarcinoma (PA) have been described in Lobund-Wistar (L-W) rats: spontaneous PAs that develop at a mean age of 26 months; and induced PAs that develop at a mean time of 10.5 months. Both are similar in many respects to the counterpart disease in man. PAs develop spontaneously, and by induction through a combination of N-methyl-N-nitrosourea (MNU)/testosterone treatments. Our investigations with L-W rats show that PA is manifested spontaneously in 26% of aged L-W rats, and by induction in approximately 90% of younger rats. It is characterized by metastatic adenocarcinoma initiated in, and expanding from, the dorso-lateral and anterior lobes, and occasionally in the seminal vesicles. It is regulated by genetic, hormonal, and age-related mechanisms. Spontaneous PAs are prevented by life-long moderate (25%) diet restriction and, in rats at risk of developing induced PA, by early treatments with estradiol, with dihydrotestosterone, with a retinoid, and by castration. While the "premalignant" stages of induced tumorigenesis are susceptible to intervention, the overtly malignant stage resists therapeutic trials with the same agents and procedures. The transition from dependency to autonomy has not yet been defined.


Animal models for the study of prostate carcinogenesis.

Human prostate carcinogenesis has been viewed as a multi-step process involving progression from low histologic grade, small, latent carcinoma to large, higher grade, metastasizing carcinoma. However, recent data suggest that a variety of pathogenetic pathways may exist. The precise etiology and pathogenesis of human prostate cancer remain largely undefined. It is difficult to investigate stages in the development of human prostate cancer, but some animal models provide opportunities in this regard. Short-term treatment of rats with chemical carcinogens produces a low incidence (5-15%) of prostate cancer, provided that prostatic cell proliferation is enhanced during carcinogen exposure. Chronic treatment with testosterone also produces a low prostate carcinoma incidence. A high carcinoma incidence can only be produced by chronic treatment with testosterone following administration of carcinogens such as N-methyl-N-nitrosourea (MNU) and 3,2'-dimethyl-4-aminobiphenyl (DMAB). Testosterone markedly enhances prostate carcinogenesis even at doses that do not measurably increase circulating testosterone. Thus, testosterone is a strong tumor promoter for the rat prostate. All such MNU- or DMAB-initiated and/or testosterone-promoted tumors are adenocarcinomas; most originate from the dorsolateral and anterior, but not ventral, prostate lobes. These tumors share a number of important characteristics with human prostate cancer. A high frequency (70%) of activation of the K-ras gene by a G35 to A mutation occurs in these carcinomas. Another high incidence prostate carcinogenesis model, representing a different pathogenetic pathway, involves chronic administration of estradiol-17 beta to rats in combination with low-dose testosterone. The resulting carcinomas are low-grade and originate exclusively from periurethral ducts of the dorsolateral and anterior prostate. While it is unknown whether testosterone is a tumor promoter in this system, preliminary studies indicate the formation of a DNA adduct in the target tissue, which suggests that estradiol-17 beta acts as a tumor initiating agent in this system. The high incidence models mentioned earlier are adequate for the study of chemoprevention of prostatic carcinogenesis. Analysis of shifts in the relative incidence of metastasizing carcinoma, grossly apparent but not-metastasizing carcinoma, microscopic-size carcinoma, and carcinoma in situ or atypical hyperplasia may allow study of the modifying effects of potential chemopreventive agents on tumor progression in these animal models of prostatic carcinogenesis.


Human prostate cancer model: roles of growth factors and extracellular matrices.

A human prostate cancer model was established by inoculating a prostate specific antigen (PSA)-producing LNCaP cell line with either prostate or bone fibroblasts. Alternatively, this human prostate cancer model can also be established by inoculating LNCaP cells with growth factor(s) (GFs) and extracellular matrix (ECM) immobilized on Gelfoam. The resulting LNCaP tumors were used to evaluate PSA production and excretion in athymic hosts. This model was also employed to examine the biochemical nature of mesenchymal cell-derived growth-promoting protein(s) and to assess the efficacy of potential chemotherapeutic agents. Because of the propensity of human prostate cancer to metastasize to the bone, this study defined a 1.0 M NaCl-eluted fraction, MS1, from the conditioned medium of a bone stromal cell line (MS) by heparin-affinity column chromatography. The growth-promoting activity was assayed both in vivo (e.g., tumor formation) and in vitro (e.g., soft agar colony formation). We found that the growth-promoting activity was trypsin- and heat-sensitive, and partially degraded by acid and dithiothreitol. Immunochemical studies indicated that the polyclonal antibody raised against MS1 blocked the growth-promoting effect elicited by the bone-conditioned media. This growth-promoting factor was found to be immunochemically dissimilar to KGF, HGF, and bFGF. However, addition of bFGF, HGF and NGF, but not aFGF, TGF beta, IGF1, IGF2, PDGF, EGF, TGF alpha and KGF, stimulated anchorage-independent growth of prostate cells, a condition closely parallel to tumor formation in vivo. We found that the MS1 fraction also contained fibronectin and tenascin but not laminin or collagen IV.(ABSTRACT TRUNCATED AT 250 WORDS)


Immunologic structure and function of the gastrointestinal tract.

Host defenses within the gastrointestinal tract exclude bacteria and other intraluminal substances, which if released into the systemic circulation, would be toxic to the body. This is accomplished via complex interactions between these external pathogens and local immune responses and nonimmunologic processes. In addition to the mechanical and chemical barriers of the nonimmunologic defense system within the gastrointestinal tract, there is an effective immunologic barrier composed of aggregated and nonaggregated lymphoid cells. Gut-associated lymphoid tissue protects the intestinal mucosa from invading pathogens by intricate pathways of antigen processing. Gut-associated lymphoid tissue also transfers protection to other secretory sites within the body through the common mucosal immune system. The integrity of both the immunologic and nonimmunologic barriers may be affected by any number of pathologic insults as well as by nutritional influences. This article reviews the structural and functional characteristics of this complex and critically important host defense system. Specific nutrient requirements of the immunologic processes are discussed.


Combined parenteral and enteral nutrition in severe trauma.

Early enteral feeding is increasingly advocated for the nutrition support of severely stressed patients. The successful use of this modality in critical illness is often limited by the patient's condition, the availability of access for feeding, and the patient's tolerance of the enteral formula. Factors such as abdominal injury or constraints on fluid volume also complicate nutrition support in this setting. Attention to a secure and well-maintained small bowel access tube and appropriate formula selection allow safe tube feeding in these patients. This case report describes the clinical course of a patient with severe chest and abdominal trauma who received enteral nutrition despite a large, open abdominal wound.


Enteral feeding in the critically injured patient.

Metabolic support is an integral component in the care of the critically injured patient. When hypermetabolism occurs, there are increases in energy demands along with changes in substrate utilization. This article reviews the prospective randomized clinical trials that were undertaken at Denver General Hospital over the past decade that address both the timing of nutritional support and the route of administration in this critically injured population. Also discussed is a review of a meta-analysis that attests to the feasibility of early postoperative enteral feeding with the possibility of decreased septic morbidity in high-risk surgical patients. With the clinical knowledge gained from these trials, an algorithm for nutritional intervention was developed that represents our current standard of practice.


Nutritional management of infants with bronchopulmonary dysplasia.

The nutritional needs of the child with bronchopulmonary dysplasia (BPD) vary significantly from those of a healthy child. To address the many special aspects of the nutritional care of the child with BPD, a nutrition management protocol was established at the University of Iowa Hospitals and Clinics. This protocol discusses caloric requirements; selection of enteral feedings; electrolyte, vitamin, and mineral supplements; growth, oral feeding advancement, and monitoring of nutritional status. Although many of the guidelines are supported by research, some are based on clinical practice. Many questions remain to be answered about the optimal nutrition therapy for these infants. One goal of this protocol is to stimulate discussion and research that will lead to a better understanding of the nutritional requirements of the BPD population.


Use of indirect calorimetry in clinical nutrition.

The tremendous variability in resting energy expenditure makes efforts to predict caloric requirements difficult. Indirect calorimetry has provided a valuable tool in assessing energy expenditure, evaluating the way in which the body uses nutrient fuel, and designing nutritional regimens that best fit the clinical condition of the patient. The many indirect calorimetric instruments available vary in their application to clinical nutrition. The best metabolic studies are achieved by controlling the testing environment, accounting for the many clinical factors that may affect measurements, and eliminating potential sources for error. Although indirect calorimetry would seem to reduce the likelihood of complications from overfeeding, its greatest effect may be in cost savings by avoiding unnecessary nutritional support and in providing a means for clinical research.


Nutrition support team recommendations can reduce hospital costs.

Providing nutrition support may be costly to hospitals under the prospective payment system. A nutrition support team, however, can be effective in controlling costs. To demonstrate the importance of the nutrition support team and to quantify the potential cost savings that can be achieved, a retrospective review of the effect of our team on hospital costs was conducted for the 12-month period of October 1989 to September 1990. The team supervises but does not regulate the use of total parenteral nutrition (TPN). During this time period, 176 patients received TPN. In 14 patients, the use of TPN was inappropriate, representing $65,349 in excess costs. After the cost of providing enteral nutrition to these patients (estimated at $2,430) was deducted, a net loss of $62,919 occurred. Nutrition support team action saved an additional $45,186 in hospital charges when recommendations to discontinue TPN were eventually heeded. Nutrition support team approval before TPN is initiated would achieve cost savings.


Nitrogen balance studies in clinical nutrition.

Nutrition support is recognized as an important cofactor in altering morbidity and mortality of hospitalized patients. Paramount in delivering proper nutrition support is the accurate determination of baseline metabolic and nutritional status, thus influencing necessary protein requirements. After nutritional intervention, routine laboratory monitoring is used to measure the efficacy and to reassess metabolic stress level. Accurate determination of nitrogen excretion (and nitrogen balance) remains the standard in prescribing and monitoring the protein and nutritional treatment regimen. This article examines nitrogen excretion determinations in the clinical setting, including proper collection techniques, laboratory measurements, and analyses and their effect upon nitrogen balance studies.


Selection of nutrition support regimens.

The selection of a nutrition support regimen should be the product of a logical, stepwise process. After an appropriate candidate is selected, the integrity and function of the gastrointestinal tract must be assessed to determine if nutrients can be administered enterally or must be given by vein. The anticipated length of therapy will help determine the type of feeding access. Long-term nutrition support requires permanent access, such as a percutaneously or surgically placed feeding tube for enteral nutrition or a tunnelled catheter or implanted port for parenteral nutrition. Formula selection for enteral nutrition, providing adequate liver and renal function, depends largely on the patient's ability to assimilate intact nutrients. The primary decision in parenteral formula selection is whether to provide the macronutrients as a mixed fuel system. The ultimate goal of nutrition support is to make a smooth transition to oral feedings while maintaining adequate nutritional intake.


Current status of home infusion therapy.

The growth of home infusion therapy has been influenced by external forces that have changed the access to and use of health care. As home infusion therapy expands into other alternate care settings, clinicians, regardless of discipline, must be cognizant of how daily clinical practice is affected by regulations, changes in legislation, and consumerism.


The substance abuser and home intravenous therapy: above all else, do no harm.

Home care therapy is being challenged by changes in patient populations and technologic advances. The selection of appropriate candidates for home intravenous therapy is a critical issue faced by health care professionals. This process is more complex when the patient has a history of intravenous drug abuse. The issues concern patient compliance, safety, ethics, and legal responsibilities. Safe care depends on the ability of the patient to demonstrate a predetermined level of competence with catheter use. The potential use of illicit drugs may influence the ability of the patient to be compliant. Ethical principles of the patient's autonomy and free choice are weighed against the health professional's sense of beneficence. Legal guidelines stress informed consent, standards of care, and adequate documentation. An exploration of each of these factors outlines the potential risks and benefits and provides a basis for making clinical judgments.