A model of inflammatory bowel disease induced by 2,4-dinitrofluorobenzene in previously sensitized BALB-c mice.

The aim of this study was to develop a model of inflammatory bowel disease (IBD) induced by colonic application of 2,4-dinitrofluorobenzene in previously sensitized BALB-c mice. During the follow-up period of 30 days we observed ulcerations, haemorrhage, necrosis, and mononuclear infiltration in the colonic mucosa of previously sensitized (experimental) and, to a lesser extent, nonsensitized (control) animals. In addition, the animals in the experimental group developed adhesions, thickening of colonic segments, stenosis, and dilatation of the colon, and some animals also developed megacolon. Oedema, mononuclear infiltration, and superficial ulcerations were observed in the ileum of experimental animals and, to a lesser extent, in the control group. In addition, the animals in the experimental group developed extraintestinal changes in the liver and spleen (that is, pericholangitis and lymphofollicular proliferation). We suggest that this model of IBD may have some value for the study of early pathogenetic mechanisms of IBD and for developing new therapeutic modalities for this condition.


Cimetidine on-demand in dyspepsia. Experience with randomized controlled single-subject trials.

Double-blind randomized controlled trials in single subjects (N of 1 RCTs) have demonstrated a beneficial symptomatic effect of cimetidine in reflux- or ulcer-like non-ulcer dyspepsia (NUD). However, spontaneous fluctuations in symptoms reduce the validity of such trials when performed as continuous trials with fixed dosages. This study was carried out to identify individual responders to cimetidine in NUD, peptic ulcer disease, and oesophagitis and to confirm the beneficial average effect of cimetidine in these clinical entities. We evaluated N of 1 multi-crossover trial designs, which compare the effects of single doses of cimetidine and placebo taken on-demand for symptomatic relief. Each trial consisted of six cimetidine (400 mg or 800 mg) and six placebo tablets randomized in successive pairs. The symptomatic effect of each tablet was measured 1/2-6 h after the intake. Outcomes were assessed by individual p values and confidence intervals. A minimal clinically important difference was defined, to assess the clinical significance as demonstrated by the confidence intervals. Thirteen of 25 patients (52%) with reflux- and ulcer-like NUD obtained individual p values below 0.20. Similarly, 7 of 9 patients (78%) with oesophagitis and 6 of 12 patients (50%) with peptic ulcer obtained such p values. On the basis of the 80% confidence intervals the corresponding numbers of subjects with clinically significant effect were six (NUD), three, and three. The combined data showed a significantly better effect of cimetidine than of placebo (p less than 0.0001) in each of the three diagnostic groups studied. Cimetidine taken on-demand may have a rapid symptom-relieving effect in dyspepsia.(ABSTRACT TRUNCATED AT 250 WORDS)


The effect of dietary yeast on the activity of stable chronic Crohn's disease.

The effect of dietary yeast on the activity of stable Crohn's disease was assessed in 19 patients. During the 1st month patients continued their usual diet (base-line period), but during the next 2 months dietary yeast was excluded except that during 1 month patients took baker's yeast capsules while for the other month they took placebo capsules. The patients' mean Pettit Crohn's disease activity index (CDAI) while taking baker's yeast (mean, 107.9; SE, 6.1) was significantly greater than during yeast exclusion (mean, 102.1; SE, 5.7; p less than 0.05). The mean of each patient's maximum CDAI during yeast exclusion (mean, 107.1; SE, 5.7) was significantly lower than those during the base-line (mean, 115.2; SE, 6.1; p less than 0.05) and baker's yeast inclusion periods (mean, 113.9; SE, 6.7; p less than 0.05). Patients with elevated yeast antibodies tended to develop a higher CDAI while receiving baker's yeast (13 of 15). These results suggest that dietary yeast may affect the activity of Crohn's disease.


Bile acid malabsorption caused by gastrointestinal motility dysfunction? An investigation of gastrointestinal disturbances in familial amyloidosis with polyneuropathy.

Gastrointestinal dysfunction due to autonomous neuropathy is a complication described in various diseases such as diabetes mellitus, multiple sclerosis, and familial amyloidosis with polyneuropathy. We present the results of a prospective investigation of bile acid malabsorption in 17 patients with familial amyloidosis by means of 75Se-labelled homocholic-tauro acid (SeHCAT). The diagnosis was in all cases verified by the DNA test for mutation of transthyretin in position 30. Small-intestinal biopsy specimens were examined for deposits of amyloid, and the presence of gastric retention was evaluated by gastroscopy. In addition, the patients were investigated for bacterial overgrowth by means of the bile acid breath test (BABT). A high frequency of abnormal BABT results (44%) was encountered. However, 65% also had abnormal low SeHCAT values, indicating bile acid malabsorption. Only two patients had abnormal BABT and normal SeHCAT results, indicating bacterial contamination of the small intestine. Bile acid losses increased with the duration of gastrointestinal symptoms. Significantly lower SeHCAT values were encountered in patients with gastric retention, whereas the occurrence of amyloid deposits in small-intestinal biopsy specimens was without effect on SeHCAT retention. Bile acid malabsorption is frequently encountered in familial amyloidosis with polyneuropathy and seems to be more closely associated with gastrointestinal motility dysfunction than with amyloid deposits in the intestinal mucosa.


Influence of smoking on basal and on vagally and maximally stimulated gastric acid and pepsin secretion.

Published data show that smokers have greater basal or peak acid and pepsin outputs, but the mechanisms underlying these effects are unknown. To confirm this and to determine whether these findings extend to, and implicate, any vagal overactivity, gastric secretions collected for 1 h basally, 1 h after 15 min of modified sham feeding (MSF), and 1 h after pentagastrin (6 micrograms/kg subcutaneously) were analyzed for acid and pepsin content in 204 subjects, 104 with duodenal ulcer (66 smokers) and 101 without (57 smokers). Maximal acid outputs (MAO, mu eq/kg/h, means +/- SEM) were higher in smokers than in non-smokers in both duodenal ulcer (DU) (623 +/- 35 versus 491 +/- 35, p less than 0.005) and non-DU (502 +/- 32 versus 376 +/- 20, p less than 0.005). Basal and MSF secretions were generally increased in smokers but, when expressed as a percentage of MAO, were not different in smokers and non-smokers (18% versus 17% and 43% versus 39%, respectively, in DU, and 13% versus 16% and 40% versus 36% in non-DU). Maximal pepsin outputs (units x 10(-2)/kg/h) were also higher in smokers than in non-smokers (DU, 129 +/- 7.9 versus 105 +/- 9.5, p = 0.05, and non-DU, 101 +/- 7.5 versus 77 +/- 10, p = 0.05). Basal and MSF secretions as a percentage of maximal pepsin output were not different in smokers versus non-smokers. Multivariate logistic regression shows that smoking was most strongly associated with MAO and sham feeding outputs, but the duration-intensity (pack-years) of smoking was associated only with elevated MAO.(ABSTRACT TRUNCATED AT 250 WORDS)


Cisapride treatment of patients with non-ulcer dyspepsia and erosive prepyloric changes. A double-blind, placebo-controlled trial.

One hundred and twenty consecutive outpatients with non-ulcer dyspepsia (NUD) and erosive prepyloric changes (EPC) were, after a 2-week placebo run-in period, randomly allocated to double-blind treatment with either 10-mg cisapride tablets or placebo three times daily for 4 weeks. The patients' global evaluation and total symptom score were significantly in favour of cisapride at 2 weeks (p less than 0.05). At 4 weeks the effect of cisapride was no longer significant (p = 0.22). Similarly, the investigators' global evaluation showed marked to moderate symptom improvement in 47% of the cisapride-treated patients as compared with 30% of the placebo-treated patients at 2 weeks. The 95% confidence interval of the difference (18%) was 0% to 35%. At 4 weeks the intergroup difference was only 10% (cisapride, 50% versus placebo 40%). Pain on awakening was the only symptom improved in favour of cisapride at 4 weeks. Thus, when patients with NUD and EPC are treated with cisapride, the therapeutic gain might vanish after the 2nd week of treatment.


Helicobacter pylori-related hypergastrinaemia is not due to elevated antral surface pH. Studies with antral alkalinisation.

It has been postulated that Helicobacter pylori-related hypergastrinaemia is due to bacterial ammonia raising antral surface pH and thus preventing acid inhibition of gastrin release. If true, the infection should not alter gastrin release at neutral intragastric pH. To test this, we have studied basal and meal-stimulated gastrin at uncontrolled pH and at pH greater than 6 in duodenal ulcer patients before and after eradication of H. pylori. The median integrated gastrin response to the meal alone was 2525 ng/l.min (range, 550-8725) before and 725 ng/l.min (range, 250-2925) after eradication of H. pylori (p less than 0.01). The corresponding values when intragastric pH was maintained above 6 were 3700 ng/l.min (range, 1900-14,100) and 1400 ng/l.min (range, 400-3400) (p less than 0.01). The median reduction in gastrin after eradication of H. pylori was thus similar when the meal was taken at uncontrolled pH (61%; range, 0-97%) and at pH greater than 6 (69%; range, 36-89%). Likewise, 5 h of gastric alkalinisation did not cause the basal gastrin values when H. pylori was eradicated to increase to those observed when H. pylori was present. These findings indicate that the hypergastrinaemia is not due to elevated antral surface pH.


Effects of acute pancreatitis on hepatic secretion of lysosomal enzymes into bile and hepatic lysosomal fragility: protective effects of a new synthetic protease inhibitor, ONO 3307.

To evaluate the effects of acute pancreatitis on hepatic function and hepatic cellular and subcellular organellar fragility, we studied 1) the hepatic secretion of lysosomal enzymes (beta-glucuronidase, beta-galactosidase, and N-acetyl-beta-glucosaminidase) into bile in the isolated perfused rat liver model; 2) the aspartate aminotransferase (ASAT), alanine aminotransferase (ALAT), and lysosomal enzyme levels in the effluent in an isolated liver model; 3) hepatic lysosomal fragility in an in vitro incubation study; and 4) protective effects of a new low molecular weight synthetic protease inhibitor, ONO 3307, against hepatic injury in doses of 2 and 5 mg/kg.h in acute pancreatitis induced by a supramaximal dose of cerulein in rats. Decreased hepatic secretion of lysosomal enzymes into bile and accelerated hepatic lysosomal fragility were observed in acute pancreatitis induced by cerulein. ONO 3307 showed a significant protective effect against this hepatic injury in acute pancreatitis, the dose of 5 mg/kg.h showing a more potent effect than the dose of 2 mg/kg.h. These results suggest that the impaired hepatic function, including depressed hepatic secretion of lysosomal enzymes, seems to be closely related to accelerated hepatic fragility and that some unknown protease, which is present in pancreatitis and is susceptible to inhibition by ONO 3307, plays a crucial pathologic role in the development of this liver injury during acute pancreatitis.


Erosive prepyloric changes in dyspeptics and non-dyspeptics in a defined population. The Sørreisa Gastrointestinal Disorder Study.

In this population-based endoscopic survey we found erosive prepyloric changes (EPC) in 38.5% of dyspeptics and 35.1% of non-dyspeptics. EPC were observed more frequently in men than in women in both groups. Occurrence of Helicobacter pylori was not associated with EPC. No common gastrointestinal symptoms were found to be associated with EPC. Endoscopic duodenitis of the duodenal bulb was found more frequently in subjects with EPC of the two highest grades than in subjects without EPC. Only the highest grade of EPC was associated with chronic gastritis. EPC were associated with cigarette smoking and, among women, also use of alcohol. We conclude that EPC constitute an endoscopic finding without relation to specific symptoms. These changes therefore do not represent a clinical entity, and it is doubtful whether this finding will give the clinician a better understanding of dyspepsia.


Influence of dehydrocholic and cholic acids on the biliary secretion of anionic polypeptide fraction, the major apoprotein of the biliary lipoprotein complex.

This work was undertaken to study the effect of intravenously infused dehydrocholate (DHCA) and cholate (CA) on lipid and anionic polypeptide fraction (APF) secretion in bile. APF is a small acidic amphipathic apoprotein closely associated with biliary lipids and bilirubin and involved in the control of bile-destined cholesterol. Rats were infused with increasing doses of DHCA (2 and 3 mumols/min/100 g b.w.) and then CA (1, 2, and 3 mumols/min/100 g b.w.). Each dose was infused for 30 min. As expected, intravenous DHCA inhibited biliary phospholipid (PL) and cholesterol secretion, and CA restored it. When DHCA was infused, the level of APF increased fourfold compared with controls. The APF/PL ratio also increased, but biliary albumin remained stable. When bile secretion was stimulated by infusion of CA, biliary APF returned to normal. These data indicate that biliary secretion of APF depends on the nature and the amount of bile salts returning to the liver, and consequently, APF can be considered a marker of bile secretion disorders.


Antrectomy does not accelerate reversal of omeprazole-induced trophic effects in the rat stomach.

The oxyntic mucosa in the rat stomach is under the influence of circulating gastrin. The histamine-producing enterochromaffin-like (ECL) cells constitute the major endocrine cell population in the oxyntic mucosa. They are notably sensitive to changes in the serum gastrin concentration and respond to long-term hypergastrinemia with hyperplasia, whereas hypogastrinemia induces hypoplasia. In the present study long-term, sustained hypergastrinemia was induced by daily treatment with a high dose of the proton pump inhibitor omeprazole. After 10 weeks omeprazole-treated and control rats were antrectomized, resulting in prompt hypogastrinemia. Antrectomy was followed by a rapid reduction of the thickness of the oxyntic mucosa and a somewhat slower reduction of the ECL cell number in both omeprazole-treated and control rats. The percentage decrease in the ECL cell number with time was similar in both groups; after 2-3 weeks the ECL cell number was half of that before antrectomy in both groups. Interestingly, however, 12 weeks after antrectomy the ECL cell number in the omeprazole-pretreated rats remained elevated compared with untreated rats. The histamine concentration of the oxyntic mucosa was markedly lowered within a week after antrectomy in both omeprazole-treated and control rats. Although antrectomy induces hypogastrinemia and although atrophy develops rapidly in the oxyntic mucosa, the omeprazole-induced ECL cell hyperplasia was not completely reversed by antrectomy during the 12 weeks of examination.


Double-blind randomized trial of bismuth subsalicylate and clindamycin for treatment of Helicobacter pylori infection.

We evaluated clindamycin and bismuth subsalicylate (Pepto-Bismol) for treatment of Helicobacter pylori infection. Patients with culture or histology positive for H. pylori were randomized to receive two tablets of bismuth subsalicylate four times daily for 4 weeks or bismuth combined with 2 weeks of 300 mg clindamycin four times daily. Clinical symptoms were recorded before and after treatment by means of visual analog scales. Patients in both treatment arms showed improvement in clinical scores for abdominal pain, heartburn, and gas or bloating. Microbiologic cure was achieved in only 1 of 11 patients treated with bismuth alone and in none of 7 treated with bismuth/clindamycin. Successful eradication of H. pylori may require combination of multiple antibiotics, as recommended at the IXth World Congress of Gastroenterology, or pharmacokinetic modulators such as H2-blockers or omeprazole.


Diagnosis of bacterial overgrowth after culturing proximal small-bowel aspirate obtained during routine upper gastrointestinal endoscopy.

The purpose of this study was to evaluate the method of obtaining aspirated fluid for culture from the small intestine through a fiberoptic gastrointestinal endoscope for diagnosing small-bowel overgrowth. The study population consisted of 10 healthy volunteers and 26 patients with various gastrointestinal problems referred for routine endoscopic examination. The material to be cultured was obtained under direct visualization approximately 25 to 30 cm distal to the pylorus or from the afferent loop (in Billroth-II patients) with a sterilized sheathed wash pipe passed through the suction channel of the endoscope. Cultures were considered positive for bacterial overgrowth if total counts of organisms were 10(5)/ml or more. All healthy volunteers and 16 of 21 unoperated patients had sterile or insignificant growth, whereas all 5 patients who had Billroth-II operations had positive overgrowth. The endoscopic method for collection of proximal gastrointestinal fluid for culture is simple and can be performed during routine endoscopy.


C3bi/CR3 is a main ligand-receptor interaction in attachment and phagocytosis of C3-coated particles by mouse peritoneal macrophages.

We investigated the relative role of C3bi-CR3 interaction in the binding and phagocytosis of EAC43 by mouse peritoneal macrophages. Anti-Mac-1 F(ab')2 markedly inhibited the binding and lymphokine-induced phagocytosis of both EAC43b and EAC43bi. Fifty per cent inhibition of attachment and phagocytosis occurred at 1 microgram/ml of anti-Mac-1 F(ab')2 in the incubation media. On the other hand, EIgG binding and phagocytosis were not inhibited at all even at a concentration of 10 micrograms/ml. Depletion of divalent cations from the incubation media abolished EAC43b and EAC43bi rosettes but not EIgG rosettes or phagocytosis. These data suggested that both EAC43b and EAC43bi binding to macrophages were mediated via CR3. Because a drastic decrease of EAC43bi rosettes was observed in the case of EAC43bi cells prepared with smaller amounts of C3, a small contamination of C3bi molecules on EAC43b, itself, cannot explain the efficient attachment of EAC43b. We propose that EAC43b on the macrophage surface can be quickly converted to EAC43bi, forming EAC43bi rosettes, and that those erythrocytes are vigorously ingested by lymphokine-activated macrophages. In accordance with this hypothesis, we demonstrated that EAC43b was converted to EAC43bi in the medium in which macrophages had been incubated.


Enhancement of the antibody response to protein antigens by specific IgG under different experimental conditions.

Specific stimulation of the antibody response to protein antigens by IgG antibodies was studied in vivo. The response to TNP-coupled keyhole limpet haemocyanin (KLH-TNP) was enhanced by a TNP-specific IgG monoclonal antibody, 7B4, as measured both in ELISA (enzyme-linked immunosorbent assay) and by ELISPOT (enzyme-linked immunospot) method. Enhancement was seen when using both high and low doses of antigen and antibody. The antibody response to TNP-coupled bovine serum albumin (BSA-TNP), but not to TNP-coupled ovalbumin (OA-TNP), tetanus toxoid (TT-TNP) or diphtheria toxoid (DT-TNP), was also efficiently augmented by 7B4. Enhancement was seen when using both high and low coupling ratio of TNP to KLH. The fact that IgG-mediated enhancement is seen under many different experimental conditions suggests that it is a physiologically relevant phenomenon. In order to enhance the response to KLH-TNP and BSA-TNP, 7B4 had to be injected while antigen was circulating in blood. This supports that IgG-mediated stimulation acts by concentrating circulating antigen into lymphoid centres.


Involvement of the avian mu heavy chain in recolonization of the bursa of Fabricius.

In the chicken, the B cells develop in a specialized organ, the bursa of Fabricius. Earlier it was shown that neonatal bursal cells treated with polyclonal anti-chicken immunoglobulin antibodies are not able to recolonize the bursa when transferred into cyclophosphamide-treated chicks. In this study, 4-day-old bursal cells were treated with different polyclonal and monoclonal anti-immunoglobulin antibodies and transferred into 4-day-old cyclophosphamide-treated chickens. Two monoclonal anti-chicken IgM antibodies, CVI-59.7 and 21-2B2, recognizing distinct epitopes of the mu heavy chain, were inhibitory. Incubation of cells with 21-2B2 antibody caused about 90% inhibition of bursal recolonization. After incubation with CVI-59.7 antibody the inhibition was 50%. The high inhibition by 21-2B2 antibody was also seen when F(ab')2 fragments of the antibody were used. These results suggest that the entry of the cells needed for bursal recolonization is inhibited almost totally by 21-2B2 antibody, or that this antibody blocks further proliferation of the cells in bursal follicles. In conclusion, we have shown that a mu heavy chain epitope is intimately involved in the recolonization of bursal follicles, and distinct epitopes of the mu heavy chain are not equally important in this process.


Aberrations in titre and avidity of serum IgM and IgG antibodies to microbial and food antigens in IgA deficiency.

The antibody levels and relative avidity of serum IgM and IgG antibodies against E. coli O antigens, poliovirus type 1 and beta-lactoglobulin were determined with enzyme-linked immunosorbent techniques in IgA deficient (IgAd) patients with frequent respiratory tract infections and healthy IgAd individuals. Healthy individuals with normal immunoglobulin levels served as controls. The IgM antibody levels against the bacterial, viral and food antigens and the IgG antibody levels against the bacterial antigens were significantly higher in the IgAd group with recurrent infections than in the group of healthy IgAd individuals. The symptomatic IgAd group had significantly higher levels of the IgG antibodies against the bacterial antigen, also when compared with controls. In contrast the healthy IgAd individuals had the highest avidities of IgM antibodies to the viral and food antigens. The high avidities of antibodies could be a compensatory host defence mechanism in IgAd. These aberrations may appear as a consequence of increased mucosal exposure in IgAd to antigens such as E. coli or beta-lactoglobulin, but presumably not to poliovirus which is only exceptionally present in the milieux. They could also be a result of the previously suggested dysregulation of antibody responses in IgAd.


Hydrocortisone treatment of BCG-infected mice impairs the activation and enhancement of antimicrobial activity of peritoneal macrophages.

The present study concerns the effect of hydrocortisone (HC) on the effector functions of Bacillus Calmette Guerin-purified protein derivative (BCG-PPD)-activated macrophages. Such activated macrophages release greater amounts of H2O2 and NO2-, inhibit the intracellular proliferation of T. gondii and kill L. monocytogenes more efficiently than resident macrophages. This activation was not fully expressed by macrophages from BCG-activated mice that had received a subcutaneous injection of HC 2 days before intraperitoneal injection of PPD, since the inhibition of the intracellular proliferation of T. gondii, the release of NO2- and the rate of intracellular killing of L. monocytogenes were lower than in macrophages from BCG-PPD-activated mice. However, treatment with HC did not impair the release of H2O2 by BCG-PPD-activated macrophages. The results show that the treatment of infected mice with HC inhibits their ability to develop adequate intracellular microbicidal mechanisms.


A family of cross-reacting proteins secreted by Mycobacterium tuberculosis.

Cross-reactions between five proteins actively secreted by Mycobacterium tuberculosis were studied by crossed immunoelectrophoresis, SDS-PAGE with immunoblotting, and ELISA using polyclonal rabbit antisera and mouse monoclonal antibodies to the purified proteins. The monoclonal antibody HBT4 was demonstrated to react with the MPT51 protein. The 85A, 85B and 85C constituents of the M. tuberculosis and Mycobacterium bovis BCG antigen 85 complex cross-react extensively, each of the components containing component-specific as well as cross-reacting epitopes. These components also cross-reacted with MPT51 and MPT64. N-terminal sequence studies revealed striking homology at the amino acid level between 85A, 85B, 85C and MPT51. MPT64 showed less homology. In addition, striking homology was demonstrated between two different stretches within the 85B sequence and indicated between three stretches within the MPT64 molecule. Thus, a family of at least four secreted proteins with common structural features has been demonstrated in mycobacteria. MPT64 may also belong to this family.


Analysis of HLA genotypes and susceptibility to insulin-dependent diabetes mellitus: HLA-DQ alpha complements HLA-DQ beta.

It is well known that certain genes in the HLA-D region confer increased susceptibility to insulin-dependent diabetes mellitus (IDDM). Previous studies have documented an increased risk associated with the HLA-DR beta chain alleles, DR3 and DR4, and the DQ beta chain allele DQB1*0302 (formerly DQw8). Since DQ alpha is also polymorphic and has been strongly implicated as the primary IDDM susceptibility locus in other races, we wanted to assess the contribution of DQ alpha to IDDM in Caucasians. This information would enable us to define more precisely the class II association with IDDM as well as gain insight into issues of cis versus trans association of DQ heterodimers in this disease. To this end, the DQ alpha genotype was determined for a large group of diabetic and normal Caucasian individuals who had been HLA-DQ beta and HLA-DR typed previously. Using the polymerase chain reaction and a set of twelve oligonucleotide probes, we determined the DQ alpha genotype of 323 patients with IDDM and 182 normal subjects. We found that certain DQ alpha alleles are decreased in the diabetic population compared with normal subjects (i.e. DQA1*0102 and *0103), while others are significantly increased in patients with IDDM (i.e. DQA1*0301 and *0501). In addition, certain combinations of DQ alpha alleles are associated with increased susceptibility to disease (i.e. DQA1*0301, *0501). These results parallel our findings at the DQ beta locus; however, because of the various associations between DQ alpha and DQ beta chains, the risks conferred by DQ alpha are generally lower than those at DQ beta. Moreover, our data indicate that, in Caucasians, no single DQ alpha allele accounts for the highest degree of susceptibility to IDDM as in other races, although DQ alpha analysis may be informative in a few cases. When done in combination, however, oligonucleotide analyses at both DQ alpha and DQ beta complement each other and provide a more complete assessment of the HLA-associated component of disease susceptibility in IDDM.


Analysis of HLA genotypes and susceptibility to insulin-dependent diabetes mellitus: association maps telomeric to HLA-DP.

There is convincing evidence that certain combinations of alleles within the human leucocyte antigen (HLA) complex, particularly within HLA-DQ, are associated with either resistance or susceptibility to insulin-dependent diabetes mellitus (IDDM). A previous study conducted on a large, well-defined group of patients demonstrated that DQB1*0302 (DQw8) conferred 'dominant susceptibility' to IDDM while DQB1*0602 (DQw1.2) conferred 'dominant protection'. The availability of this population enabled us to further assess susceptibility associated with other class II alleles in an effort to map an outside HLA boundary of disease association. Using a group-specific polymerase chain reaction protocol and a series of oligonucleotide probes which define over twenty DP beta alleles, we studied 286 unrelated Caucasian patients with IDDM and 184 normal subjects. We found that while several alleles are increased (DPB1*0201, DPB1*0301, DPB1*0402) or decreased (DPB1*0101, DPB1*0202) in the diabetic population compared with the normal subjects, the HLA association with IDDM is considerably weaker at the DP locus. These data define the centromeric boundary for the HLA-associated susceptibility gene in IDDM, localizing susceptibility to the region telomeric to HLA-DP up to and including HLA-DQ.


Peptide binding to class I molecules of the major histocompatibility complex on the surface of living target cells.

Molecules encoded by the class I major histocompatibility genes bind short (nonameric) peptides produced by intracellular proteolysis of antigens. These complexes formed intracellularly are then expressed on membranes of target cells and recognized by the antigen receptor of cytolytic T cells. No binding of externally added peptides could so far be monitored directly on the antigen presenting cells, although cytotoxicity experiments and indirect binding assays provided evidence for its existence. Here we report experiments where specific binding to class I molecules, of externally added peptides, has been monitored on living cells. N-terminal biotin-labelled Kd-restricted peptides (residues 147-155, residues 147-158, and an analogue lacking the arginine at position 156, derived from the sequence of the influenza A virus nucleoprotein) were incubated with murine H-2Kd mastocytoma cells (line P815) at 4 degrees C. The binding on surface of live, intact cells was then demonstrated fluorometrically via the interaction of a streptavidin-phycoerythrin conjugate with the biotin-labelled peptides. Thus, this binding does not involve processing, and its specificity in terms of peptide structure was established by competition with the respective unmodified peptides. The specificity of binding to class I molecules was demonstrated by blocking experiments using monoclonal antibodies specific for H-2Kd. Finally, a correlation was observed between the results of peptide binding measurements and those of cytotoxicity assays.


Nucleotide sequence analysis of rheumatoid factors and polyreactive antibodies derived from patients with rheumatoid arthritis reveals diverse use of VH and VL gene segments and extensive variability in CDR-3.

The heavy and light chain nucleotide sequences of 17 monoreactive and polyreactive rheumatoid factors largely derived from the inflamed synovial tissue of two patients with rheumatoid arthritis are described. Some of these sequences have been the subject of a previous report from our laboratories. Additionally, a few rheumatoid factors from the peripheral blood of patients with systemic lupus erythematosus and Sjogren's syndrome as well as a normal individual are included. A review of our previous results as well as the new data provided within this paper lead to the following major conclusions: (1) Rheumatoid factors and polyreactive antibodies derive from a diverse array of VH and VL gene segments; (2) While many rheumatoid factors and polyreactive antibodies are direct or nearly direct copies of germline genes, some show clear evidence of somatic mutation; (3) The CDR3 of all of these antibodies is extraordinarily diverse in length and composition. Certain 'restrictions' do appear in this very large sample: (a) the polyreactive antibodies are exclusively lambda, and (b) there seems to be a preponderance of a particular subset of VH3 genes beyond that one would expect based on random utilization.


[Elbow dysplasia in the dog].

Elbow dysplasia (ED) is a common developmental malformation in many breeds over 20 kg bodyweight. It may affect as many as 50% of all dogs within a breed. Arthrosis and poor performance may result. The most common forms of ED are fragmented medial coronoid process, osteochondrosis of the medial humeral condyle and loose anconeal process. There is evidence for the existence of a hereditary disposition for osteochondrosis in Labrador retrievers. In Sweden selection of ED-free dogs for breeding resulted in reduction of frequency and degree of severity of ED in the offspring. Adoption of a similar breeding program for Switzerland is suggested.


[Abdominal sonography in primary diagnosis of blunt abdominal trauma].

200 patients with blunt abdominal trauma were scanned by ultrasound primarily. 152 showed a normal sonographic examination. In 24 patients an organic injury was visualised. These 20 splenic injuries, 2 lesions of the kidney, 1 splenic and renal lesion and 1 hepatic and splenic rupture were confirmed by CT in 9 cases, by laparotomy in 9 cases, by sonographic follow-up in 2 cases. 23 patients showed an intraabdominal fluid collection, in 16 patients a decrease was seen by ultrasound. 7 patients were directly operated on because of a visible increase of intraabdominal fluid. The lesions consisted of 3 hepatic ruptures, 2 retroperitoneal bleedings. Ultrasound is a reliable tool in the diagnosis of blunt abdominal trauma on the day of admittance and in the evaluation of injuries in respect of operative or conservative management.


[Sonography in salmonella enterocolitis].

27 patients suffering from salmonella enterocolitis--24 proven by stool cultures, 3 confirmed serologically--were examined for ultrasound findings. In 81% the left side gut wall was concentrically thickened up to 7 mm (5-11). Further sonographic findings were: Less demarcated gut wall layers in 33%, hypoechoic gut wall in 48%, polypoid mucosa thickening in 33%. In individual cases enlarged mesenteric lymph nodes, splenomegaly, and ascites were seen. Sonographic changes correlated well with clinical results in respect of the intensity of the illness.


[Sonography of pancreatic cancer].

The aim of this retrospective study was to test the quality of pancreatic sonography in a hospital without CT. Out of 25 patients 21 were assessable. We made the correct diagnosis in 76.2% (n = 16) of the cases. The tumour size was between 25 and 60 mm. 20 tumours showed a relatively hypoechoic mass. A dilatation of biliary ducts could be seen in 87.5%. Metastasis of lymph nodes we could only detect in 38.5%, liver metastases in 64.5%. The sensitivity increases with the experience of the examiner, but lot of time is necessary. It is difficult to make a differential diagnosis between carcinoma and pancreatitis. In this cases, CT shows better results. In spite of improvements in sonography, early cancer still is a diagnostic problem.


[Cryptogenetic ascites. Attempts at original pathophysiologic explanation of a monomorphic sonographic image pattern].

In 15,645 consecutive ultrasound examinations of the abdomen (1986 to 1988), free fluid in the peritoneal cavity was found in 247 patients by internal trial during 397 sessions (= 2.5%). Most frequent basic diagnosis for the reason of this symptom were tumorous diseases (99 patients corresponding to 40.1%), cirrhosis of the liver (52 patients corresp. to 22.1%) and heart failure (31 patients corresp. to 12.6%, among these complex gayprooft myocardial insufficiency 24, right heart failure 7). Ovarian cysts or cystomas (7), acute/chronic-recurrent pancreatitis (6), Crohn's disease (3), infections (3), rheumatoid disorders (3), nephrotic syndrome (2), and extra-uterine pregnancy (2) were more rarely represented. In 23 patients (corresp. to 9.3%) the cause of an ascites remained obscure. Among these, a high prevalence of the female sex in the premenopausal age was remarkable with a score of 20:3 (statistically significant difference in terms of the other patients of our group). This observation suggests that an ovarian factor plays a role in the development of ascites in the absence of other evident causes. The literature implies that endometriosis is rather prominent, followed by oligosymptomatic infections or inflammatory diseases.


[Representation of texture parameters of B-mode sonograms in image form].

The possibility is exemplified of visualising important parameters of the statistical texture describing the echogenicity of ultrasound B-mode scans of the liver as a composite image. The two relevant parameters are gray level and standard deviation of gray levels. These were selected because they offer the best criterion to differentiate between tissues. In a composite image, the mean gray level is represented by the luminosity information, whereas the other main parameter of the gray-level histogram, the standard deviation of gray levels, is represented by the colour information. These composite images show texture parameters of the whole scan and allow an efficient documentation of the same.


[Sonographic evaluation of changes in testicular tissue by ultrasound spectroscopy].

Experimental investigations were carried out under in vitro conditions on 25 normal human testicular specimens and on 60 pathological testicular specimens to ascertain the ultrasound attenuation using an ultrasound spectroscopic measuring technique. The ultrasound attenuation was established by calculating the ultrasound attenuation coefficient alpha. The average values of ultrasound attenuation (alpha) in normal testicular tissue were distinctly lower than in pathologically altered testicular specimens. A comparison of the various pathologically altered testes showed higher attenuation in the case of malignant neoplasms whilst the highest average values of wore recorded for non-neoplastic pathological alterations in the testicular tissue. The results of the investigations show that certain alterations in the tissue can be ascertained by ultrasound spectroscopy. The analysis of further acoustic parameters in future investigations, such as ultrasound back-scattering and velocity, along with the recording of ultrasound attenuation, gives scope for improved assessment of the tissue. Thus ultrasound spectroscopy increases the sonographic accuracy acquired through analysis and the weighing up of symptoms of tissue dependent ultrasound parameters.


[B-scan ultrasound findings in the carotid bifurcation area of hemodialysis patients].

Using B-mode ultrasonography, the frequency of carotid atherosclerosis was investigated prospectively in 50 patients on maintenance haemodialysis compared to healthy controls. The patients showed significantly more atheromatous plaques at the carotid bifurcation, as well in the internal and external carotid artery (chi-square-test, p less than 0.05). There was no statistical difference between normotensive patients on haemodialysis and the control group, but hypertensive patients showed statistically significant more plaques of the cervical vessels (chi-square-test, p less than 0.05). Therefore, atheromatous plaques in haemodialysis patients appear to be due to hypertension rather than to maintenance dialysis.


[Possibilities and limits of biplane transesophageal echocardiography in dissection of the thoracic aorta].

Dissecting aneurysms of the thoracic aorta can be rapidly and accurately diagnosed by transoesophageal echocardiography. The recent advent of the transoesophageal echocardiographic probe with transverse and longitudinal imaging transducers that add orthogonal viewing planes is an important advance in the evaluation of both the anatomic and haemodynamic status of the patient. It allows a still better understanding of the pathologic changes and therefore helps in surgical decision making. With the capabilities of colour flow Doppler, biplane transoesophageal echocardiography proves to be an ideal tool for the preoperative confirmation of the suspected diagnosis, intraoperative assessment and post-operative ambulatory follow-up and should be applied whenever possible.


[Hypogangliosis of the sigmoid colon: possibilities of sonographic diagnosis].

This case report concerns a 53-year old woman suffering from recurrent spastic pain and a painful "resistance" in the left lower bowel for the last 30 years. Earlier clinical investigations including endoscopy and laparoscopy did not yield any results. In a recent investigation, only sonography showed wall thickening and an echo-poor wall pattern of the sigmoid colon indicating this to be the site of painful resistance. Resection of the sigmoid colon was performed. Histologically a slight hypogangliosis of the colon and muscular hypertrophy were detected (as the only pathological signs). The patient was free from symptoms since operation. This case report proves that ultrasound may yield pointers (or confirm the diagnosis) in unclear abdominal diseases.


[Functional colonic pain. An important clinical and sonographic differential diagnosis].

Functional abdominal pain may often be sonographically attributed to the colon. Typically a segment of the colon is painful at direct palpation, but the wall is not thickened. The contractions between the haustra are often marked. The haustra are clearly outlined and cast acoustic shadows. If the patient also experiences spontaneous pain in this region, functional colonic pain, explained as spasms of the muscle coat, may be assumed. Clinically there are often other symptoms of the irritable bowel disease or a spastic constipation. In daily practice functional colonic pain is as frequent as dyspepsia. Differential diagnosis includes intestinal (peptic ulcer, Crohn's disease, appendicitis, diverticulitis, colon cancer) and extraintestinal diseases (e.g. of the gallbladder, pancreas and female adnexes).


[Sonomorphology of stress cholecystitis].

Acute acalculous cholecystitis is a well-known complication in postoperative and particularly in severely traumatized unit patients. All that is known so far of "stress"-cholecystitis is based on episodic case reports and retrospective analyses. An incidence between 0.5 and 4.2%, a complicated clinical course and a lethality up to 75% have been reported. In intensive-care unit patients a clinical diagnosis of suspected acute cholecystitis is rarely reliable; greater reliance is placed on the ultrasound findings as seen in our prospective study. According to the literature, the established ultrasound criteria of cholecystitis include: hydrops, thickening of the gallbladder wall, sludge, subserosal oedema, pericholecystic fluid collection and fragmentation of the gallbladder wall. Other factors, however, may also lead to morphological changes of the gallbladder, and hence there is no agreement about the definitive sonomorphology of this entity. The variability of sonomorphological criteria is reviewed and compared to the results of a series of our own.


Human genome project.

Genome n. [gene plus chromosome] the complete set of chromosomes containing all of the genes of an organism. For man this set of 46 per cell stretches to a 6 foot strand of DNA. Within this string of 3 billion nucleotide bases are 100,000 genes. Utilizing a 4 letter alphabet (Adenine, Guanine, Cytosine, Thymine), genes provide the blueprint for the amino acid sequence of structural protein (cell membrane, connective tissue, etc) or functional protein (hormones, enzymes, transmitters, etc). DNA replication guarantees exact gene copies and chromosome meiosis and crossing over guarantees varied gene combinations. This forms the basis for the similarity and the diversity of all of humankind: the similarity needed to perpetuate successful genes and the diversity needed for genes to respond to the weeding out process of evolution.


Genes, patents, and product development.

In the past year, the National Institutes of Health (NIH) has filed patent applications on more than 2750 partial complementary DNA sequences of unknown function. The rationale for the filings--that patent protection may be necessary to ensure that private firms are willing to invest in developing related products--rests on two premises: first, that NIH may obtain patent rights that will offer effective product monopolies to licensee firms, and second, that unless NIH obtains these rights now, firms will be unable to obtain a comparable degree of exclusivity by other means, such as by obtaining patents on their own subsequent innovations. Neither premise is clearly wrong, although both are subject to doubt in view of statements from industry representatives that the NIH patenting strategy will deter rather than promote product development.


Genome research: fulfilling the public's expectations for knowledge and commercialization.

This article provides a historical perspective for the patenting of gene sequences and describes the fundamentals and evolution of patent law. It summarizes federal technology transfer law and policy and assesses the impacts of patenting on academic research. The patentability of gene sequences is then considered along with potential impacts that published sequence data may have on obtaining patent protection for downstream products. Industry's position on gene patenting is summarized and perspectives from the emerging public record on these issues are presented. The article discussing points at which the filing of patent applications and the licensing of patents may be appropriate. It concludes that technology transfer policies for genome research must be adopted carefully so that they remain viable in a time of rapid technological change.


Patents on random complementary DNA fragments?

The proposal by the National Institutes of Health (NIH) to patent products resulting merely from sequencing the human genome is a mistake: at worst, it is wrong in patent law; at best, it relies on deficiencies in law concerning what is "useful" as a requirement for patents. The proposal is symptomatic of a problem besieging biotechnology--attempts to control the raw material of scientific experimentation before research has determined the practical value of such material--that needs curing on many fronts. Corrective measures are proposed for adoption by the Executive branch, the Congress, and the courts.


Internal stark effect measurement of the electric field at the amino terminus of an alpha helix.

The strengths of electrostatic interactions in biological molecules are difficult to calculate or predict because they occur in complicated, inhomogeneous environments. The electric field at the amino terminus of an alpha helix in water has been determined by measuring the shift in the absorption band for a covalently attached, neutral probe molecule with an electric dipole moment difference between the ground and excited electronic states (an internal Stark effect). The field at the interface between the helix and the solvent is found to be an order of magnitude stronger than expected from the dielectric properties of bulk water. Furthermore, although the total electric dipole moment of the helix increases with length, the electric field at the amino terminus does not.


Pseudo--half-knot formation with RNA.

A pseudo--half-knot can be formed by binding an oligonucleotide asymmetrically to an RNA hairpin loop. This binding motif was used to target the human immunodeficiency virus TAR element, an important viral RNA structure that is the receptor for Tat, the major viral transactivator protein. Oligonucleotides complementary to different halves of the TAR structure bound with greater affinity than molecules designed to bind symmetrically around the hairpin. The pseudo--half-knot--forming oligonucleotides altered the TAR structure so that specific recognition and binding of a Tat-derived peptide was disrupted. This general binding motif may be used to disrupt the structure of regulatory RNA hairpins.


Combining experimental information from crystal and solution studies: joint X-ray and NMR refinement.

Joint refinement of macromolecules against crystallographic and nuclear magnetic resonance (NMR) observations is presented as a way of combining experimental information from the two methods. The model of interleukin-1 beta derived by the joint x-ray and NMR refinement is shown to be consistent with the experimental observations of both methods and to have crystallographic R value and geometrical parameters that are of the same quality as or better than those of models obtained by conventional crystallographic studies. The few NMR observations that are violated by the model serve as an indicator for genuine differences between the crystal and solution structures. The joint x-ray-NMR refinement can resolve structural ambiguities encountered in studies of multidomain proteins, in which low- to medium-resolution diffraction data can be complemented by higher resolution NMR data obtained for the individual domains.


Mechanisms of action of cyclosporine and effects on connective tissues.

Cyclosporine is a potent immunomodulatory agent with an increasing number of clinical applications. Its major mode of action is inhibition of the production of cytokines involved in the regulation of T-cell activation. In particular, cyclosporine inhibits the transcription of interleukin 2. Although cyclosporine's major actions are on T cells, there is some evidence that it produces direct effects on other cell types. Its immunosuppressive action is closely linked to its binding of cyclophilin, a member of a family of high-affinity cyclosporine-binding proteins widely distributed in different cell types and in different species. The cyclophilins have been shown to have peptidyl-prolyl cis-trans isomerase enzyme activity that is blocked by cyclosporine. Although this may be a factor in cyclosporine's selective inhibition of cytokine gene transcription, it is still unclear whether inhibition of this activity is the mechanism through which cyclosporine exerts its effects on target cells. The ubiquitous presence of cyclophilins raises the question of why cyclosporine has major effects on T cells. Perhaps the critical proteins affected are transcriptional regulators restricted in their tissue distribution. The effects of cyclosporine on T cells and, directly or indirectly, on connective tissue cells, all of which can produce a range of cytokines, are of interest in relation to the tissue changes that occur in such inflammatory conditions as rheumatoid arthritis.


The paradox of effective therapies but poor long-term outcomes in rheumatoid arthritis.

Treatment of rheumatoid arthritis (RA) presents a paradox: Many effective therapies are extensively documented in numerous clinical trials, but all long-term studies from clinical settings indicate that most patients with RA have progressive disease. This paradox may be explained in part on the basis of four observations: (1) Results of therapies for RA have been evaluated primarily according to clinical trials over short periods rather than according to long-term clinical observations over many years; (2) increased mortality rates in RA have not been widely recognized because RA is not included on death certificates of more than half of the patients who die with this disease; (3) mortality in RA generally has been attributed to causes unrelated to RA or to drug toxicity, but higher mortality in specific patients is predicted primarily by more severe clinical status; and (4) published reports indicating an optimistic prognosis in RA have been based on epidemiological studies rather than on patients in clinical settings. In epidemiological studies of large populations, 75% of individuals who meet the 1958 American Rheumatism Association (ARA) criteria for RA have no evidence of disease 3 to 5 years later; in contrast, in clinical settings more than 90% of patients with RA have evidence of disease 3 to 5 years later, generally with progression.


Prevention of adjuvant arthritis by cyclosporine in rats.

The effect of cyclosporine A during the development phase of adjuvant arthritis was studied in 40 female rats. Five groups of eight animals each received oral cyclosporine, 2.5, 5, 10, 20, or 30 mg/kg daily for 30 days. Also, eight normal and eight diseased rats served as placebo controls. At the time of inoculation of the adjuvant suspension on day 0, measurement of disease parameters (paw swelling and vertebral density) was started concomitantly with beginning of therapy. On completion of the study, the animals were killed, and after measurement of total skeletal and segmental (hind legs and caudal spine plus two caudal vertebrae) calcium, the two assessed vertebrae and both femoral condyles were removed for histomorphometric evaluation (vertebrae) and for estimation of glycosaminoglycan (GAG) content of cartilage. Blood for osteocalcin determinations also was taken at term from control and untreated arthritic rats and from animals that had received 10 mg/kg cyclosporine. Treatment with 2.5 mg/kg was ineffective, but doses between 5 and 20 mg/kg prevented the development of articular and osseous lesions. The 20 mg/kg dose showed no better effect than 10 mg/kg. This was shown by the absence of inflammation and the presence of normal condylar GAG and total mineral content in the areas screened. Untreated animals showed marked reductions in all of these parameters. The 30 mg/kg dose was effective in blocking the GAG loss, but significant reductions in bone density and trabecular volume were seen. There was a close correlation between GAG and bone density values, suggesting a common causal relationship. Circulating osteocalcin was significantly elevated in the untreated animals with adjuvant arthritis.(ABSTRACT TRUNCATED AT 250 WORDS)


Cyclosporine in rheumatoid arthritis: documented efficacy and safety.

The experience from eight open studies and five controlled trials of cyclosporine in rheumatoid arthritis is reviewed. A therapeutic approach characterized by low initial doses and slow upward titration appears to minimize the toxicity while retaining sufficient amounts of the efficacy seen with higher doses, although the onset of benefit is slower. In short-term studies, renal dysfunction and other side effects appear to be reversible. However, studies of combinations of cyclosporine and other slow-acting agents, long-term studies, and more renal biopsy specimens are needed to determine the appropriate use of this agent. Cyclosporine holds promise as an important addition to the therapeutic armamentarium for patients with rheumatoid arthritis.


Cyclosporine in rheumatoid arthritis: beyond experimentation.

The potential for combined therapy in rheumatoid arthritis is rapidly increasing considering the recent development of various new treatment modalities. However, an aggressive effort must be made to stage patients according to various clinical and immunological parameters. Only then can appropriate combined therapy be used effectively in this disease process. The development of such combined therapy could expand into other diseases such as scleroderma, systemic lupus erythematosus, and multiple sclerosis.


Cyclosporine: nephrotoxic effects and guidelines for safe use in patients with rheumatoid arthritis.

Renal abnormalities occur frequently in patients with rheumatoid arthritis; they may be complications of the rheumatoid disease process itself (amyloidosis) or may result from various therapies including gold compounds, D-penicillamine, analgesics such as aspirin or phenacetin used long term, and nonsteroidal anti-inflammatory drugs. Cyclosporine, a highly effective immunosuppressive agent currently under investigation as a treatment for RA, is also known to produce renal dysfunction. Some forms of functional and structural tubular changes appear readily reversible. Others associated with renal vasculopathy and interstitial fibrosis can lead to irreversible nephrotoxicity. A clear understanding of the pharmacology, drug interactions, and types of renal side effects encountered with cyclosporine can lead to a reduction of adverse renal reactions. Similarly, an understanding of which patients are at high risk for renal dysfunction can lead to safer and more efficacious use of this potent immunosuppressive agent.


[The effect of various sterilization procedures on the osteoinductive properties of demineralized bone matrix].

To minimize potential infection following the transplantation of allogeneic bone, extremely rigorous selection of donors and careful processing and storage of samples are required. Other major problems related to allogeneic transplants, such as reduced osteogenic properties and immunological reactions, led to the development of demineralized bone matrix (DBM). This osteoinductive bone extract is largely free of antigens and is easy to produce. However, to eliminate the potential risk of infection, DBM should be sterilized prior to implantation. The purpose of this study was to investigate the influence of different sterilization techniques on the osteoinductive properties of DBM. A series of 76 cortical defects (drill holes) 0.6 cm in diameter in the tibiae of 11 Merino sheep were filled with DBM in addition to autogeneic and allogeneic cancellous bone. Prior to implantation DBM was sterilized by autoclaving, gamma irradiation, or application of ethylene oxide or ethyl alcohol. A further 12 drill holes were left empty as controls. The formation of new bone was examined 3 and 6 weeks postoperatively, using histological, fluorescent-optical and microradiographical techniques. The amount of newly formed bone was also quantified. Apart from autoclaved DBM all matrix grafts showed excellent new bone formation following sterilization, by far exceeding the formation with allogeneic cancellous bone.


[Standardized ultrasound study with computer-assisted documentation of findings in diagnosis of polytrauma patients].

Based on the results of a prospective trial to establish the value of routine ultrasound examination in cases of polytrauma or blunt abdominal trauma, we report on our standard ultrasound examination and computer assisted documentation of the findings. Between May 1988 and December 1990 we examined 233 patients with polytrauma or blunt abdominal trauma. The results were compared with those of abdominal lavage (n = 47) performed during the same period. We found a sensitivity of 100% and a specificity of 99.5% for the ultrasound findings and a sensitivity of 80% and a specificity of 100% for the abdominal lavage. We conclude that ultrasonography should be the first diagnostic procedure used in the emergency room in cases of polytrauma and blunt abdominal trauma.


[The problem of the closed abdominal injury in polytrauma patients].

The histories of 66 patients with blunt abdominal trauma requiring surgery in the period from 1985 to 1989 were analysed. The patients were divided into three groups on the basis of the other injuries present. Group I, isolated blunt abdominal trauma and blunt abdominal trauma with slight concomitant injuries (18 patients, ISS 17.17 +/- 1.40); group II, blunt abdominal trauma with severe concomitant injuries but without craniocerebral trauma (23 patients, ISS 29.34 +/- 1.45); and group III, blunt abdominal trauma with severe concomitant injuries and an additional craniocerebral trauma (25 patients, ISS 31.08 +/- 1.27, GCS: 10.04 +/- 0.88). Initially, the diagnosis was made in 23 cases by means of diagnostic peritoneal lavage and in 43 cases by means of sonography. The subsequent laparotomy revealed the ultrasound findings to have been false-positive in 3 cases. No false-negative ultrasound findings were demonstrated at all. Peritoneal lavage, on the other hand, was found to have yielded false-negative and false-positive findings in 2 cases each. Counting from the time of admission, the time up to diagnosis of the intra-abdominal injury was 85 +/- 14.3 min in group I, 82 +/- 9.9 min in group II, and 86 +/- 12.9 min in group III. Thus, the presence of severe additional injuries did not lead to any significant delay in the diagnosis of blunt abdominal injury requiring surgery. The total mortality rate was 18.18% (group I, 11.1%; group II, 21.7%; group III, 20.0%). Six patients died in the acute phase and a further six patients during their stay on the intensive care ward.


[Hyperextension somersault trauma].

Neurological failure can occur as one feature of hyperextension trauma of the cervical spine. Apart from predisposing factors, such as dorsal osteophytes and congenital spinal stenosis, an acute narrowing of the spinal canal caused by a hyperextension somersault trauma can cause such a trauma. We observed three cases of paraplegic syndrome resulting from hyperextension somersault trauma of the cervical spine. Fast recovery from the symptoms within 12 h indicates vascular damage. The mechanism of the accident is shown with reference to clinical and experimental investigations. Hyperextension somersault trauma is characterized by a plunge from a low height, with the danger of somersaulting of the body and impact at the forehead while the head is retroflected. For this reason, extension treatment ought to be contraindicated if an accident of this kind has happened. Emphasis should be placed on adequate positioning of the patient.


[Humerus reconstruction after gunshot fracture].

High-velocity bullits can cause severe blast injuries with shattering and defects of the large bones. Initial external fixation is followed by rebuilding of the bone, which is difficult due to concomitant infection, poor revascularization and lack of a suitable bone bed. A case report of an injured African soldier shows the follow-up and difficulties of reconstruction of the shattered humerus by repeated spongious bone grafting. After successful remodeling of the bone, external fixation is followed by ASIF dynamic compression-plate osteosynthesis.


[Technique and results of modified percutaneous bore wire osteosynthesis of the distal radius].

A modified technique for percutaneous K-wire pinning of distal radius fractures is presented. With this method, three to four K-wires are introduced from the radial styloid process towards and through the dorsal, volar and ulnar proximal cortical wall, respectively. After the fracture fragments have been demonstrated to be stable, the wires are cut, bent over and fixed. Then a dorsal plaster splint is applied, which should be worn for 4-6 weeks, depending on whether or not there is a dorsal comminution zone. Fifty-five patients have been operated on by this method. At follow-up 6 months after the operation, no secondary dislocation, wire migration, infection, Sudeck syndrome or functional disturbance was seen. The advantage of this method is emphasized as compared with the usual, previously published method.


[Injury of the palmar fibrocartilage of the proximal interphalangeal joint of the long finger. Treatment and results within the scope of follow-up].

In 155 out of 389 patients with lesions of the fibrocartilage on the proximal interphalangeal (PIP) joint of the fingers, who were treated between January 1989 and 31 December 1989, a radiological and clinical follow-up was done after a mean interval of 1.5 years. In 82% a palmar lip fracture was diagnosed; the remaining 18% were attributed to a ligamentous lesion of the palmar fibrocartilate because of the clinical findings and negative X-ray results. Very good or good therapeutic results were achieved in 95%. Immobilization of the extended PIP joint for 2-3 weeks by a fingercast or plaster splint turned out to be the treatment of choice; surgical intervention was not indicated in any of these cases.


[Reconstructive interventions of the posterior cruciate ligament--experimental studies of isometric aspects. Part I: Studies of a string model].

In six intact cadaveric knees, we measured how the distance between six selected points in and around the femoral and tibial attachment area of the posterior cruciate ligament (PCL) changes with knee flexion. After complete removal of the PCL, 2-mm drill holes were made at the selected points. Each femoral point was measured against each tibial point using a heavy suture that was passed through the drill holes. The proximal end of the suture was fixed to the lateral aspect of the femur. The distal end of the suture was attached to a measuring unit. The changes in femorotibial distance were measured during flexion from 0 degrees to 110 degrees in 10 degrees steps. The tibial drill hole locations had only a minor effect on the changes in femorotibial distance. The most isometric point was located in the centre of the posterior intercondylar area. The femoral locations of the drill holes were the primary determinant of whether the distance increased, decreased or remained nearly constant. According to our results the most isometric femoral point is located at the posterosuperior margin of the anatomical PCL attachment. Using the tibial isometric point as a reference, the femoral points positioned anterior or posterior to the isometric point produced considerable changes in the femorotibial distance upon knee flexion. The anterior point led to an increase of about 7-8 mm at 110 degrees of flexion, the posterior point to a decrease of the same extent. Much smaller changes in femorotibial distance resulted from the points located superior or inferior to the femoral isometric point.(ABSTRACT TRUNCATED AT 250 WORDS)


[Reconstructive interventions of the posterior cruciate ligament--experimental studies of isometric aspects. Part II: Studies of the posterior cruciate ligament replacement model].

Isometric positioning of the posterior cruciate ligament (PCL) graft is important for successful reconstruction of the PCL-deficient knee. This study documents the relationship between graft placement and changes in intra-articular graft length during passive range of motion of the knee. In eight cadaveric knees the PCL was identified and cut. The specimens were mounted in a stabilizing rig. PCL reconstruction was performed using a 9-mm-thick synthetic cord that was passed through tunnels 10 mm in diameter. Three different femoral graft placement sites were evaluated: (1) in four specimens the tunnel was located around the femoral isometric point, (2) in two specimens the tunnel was positioned over the guide wire 5 mm anterior to the femoral isometric point, (3) in two specimens the tunnel was positioned over the guide wire 5 mm posterior to the isometric femoral point. In all knees only one tibial tunnel was created around the isometric tibial point. The location of the isometric points was described in part I of the study. The proximal end of the cord was fixed to the lateral aspect of the femur. Distally the cord was attached to a measuring unit. The knees were flexed from 0 degree to 110 degrees, and the changes in the graft distance between the femoral attachment sites were measured in 10 degrees steps. Over the entire range of motion measured the femoral tunnels positioned around the isometric point produced femorotibial distance changes of within 2 mm. The anteriorly placed tunnels produced considerable increases in femorotibial distance with knee flexion, e.g. about 8 mm at 110 degrees of flexion.(ABSTRACT TRUNCATED AT 250 WORDS)


[Intra-articular calcaneus fracture. Classification in CT as a prerequisite for therapeutic decision and quantitative comparison].

Whether conservative or operative management is selected for intra-articular fractures of the os calcis depends on subjective factors and on the surgeon's experience. There is no classification available that allows ranking of such fractures according to the extent of destruction and the degree of dislocation at the same time. CT scans of 44 calcaneal fractures have been used to elaborate a new classification system for calcaneal surfaces. According to the involvement of joint surfaces, especially of the posterior facet, the degree of dislocation and the number of fragments of the posterior facet, six classes are defined. Within each class of fracture, the formation of "steps" in the posterior facet, widening of the heel, loss of height and deviation of axes are quantified. The new classification provides an instrument for use in the evaluation of joint destruction and dislocation. It helps to provide an objective basis for decisions between functional treatment and open reduction with internal fixation and for prospective analysis of fracture treatment.


The periphysis and its effect on the metaphysis: I. Definition and normal radiographic pattern.

The zone of Ranvier and the ring of LaCroix, together with the membranous bone bark they produce, are termed the periphysis in order to emphasize their normal effect (the metaphyseal collar) on the metaphysis of the infant and young child. In the first 7 years of life, the normal collar at the wrist is 1-3 mm wide. The step-off between the metaphyseal collar and the curvilinear metaphysis, at the margin of the periphysis, should not be mistaken for abuse fracture. The periphyseal bone bark may be radiologically visible at the edge of the physis at the distal ulna in 9% of infants and should not be mistaken for fracture or rickets.


Plain radiographic predictors of survival in treated Ewing's sarcoma. IESS Committee.

We analyzed 16 radiographic features of primary Ewing's sarcoma in 342 patients from the IESS 7299 (Intergroup Ewing's Sarcoma Study) for prognostic significance. Of these, 3 features demonstrated a statistically significant relationship to survival: maximal tumor dimension, tumor location, and an appearance of honey-combing within the lesion. Those individuals with primary lesions centered in the pelvis, femur, or humerus had a worse survival rate than those with lesions centered elsewhere. Similarly, we observed an inverse relationship between the greatest dimension of the osseous portion of the lesion and survival. The radiographic finding of honeycombing also showed a statistical association with improved survival. However, this feature was observed infrequently, and its significance should be assessed further. Otherwise, no other feature that we analyzed showed any relationship to patient prognosis.


Usefulness of an acoustic edge artifact in assessment of the Ilizarov corticotomy interval.

Thirty-three ultrasound examinations of the corticotomy interval of patients undergoing Ilizarov procedures were retrospectively evaluated for the presence or absence of an acoustic edge artifact. This artifact, consisting of a fine anechoic band, has been previously described in phantom models and is presumed to be due to phase cancellation effects. We demonstrated this artifact in 8 of 33 examinations. The artifact proved helpful in identifying the location of the corticotomy margin, even when this margin was obscured by the presence of developing periosteal new bone. Attention to technical factors is, however, important. We believe that this artifact may have a useful role in the routine monitoring of the Ilizarov patient.


Ultrasonography after hip arthroplasty.

Ultrasonography was performed in 55 patients who had total Charnley hip arthroplasties. Effusions were identified in 19 patients and confirmed in all but 3 by arthrocentesis or at surgery. Aspirations were performed in 5 and demonstrated infection in 2. It is concluded that ultrasound is a valuable noninvasive method for assessing painful hip arthroplasty. It can demonstrate the presence of effusion, which should be aspirated to exclude infection.


Proliferative periosteal processes of phalanges: a unitary hypothesis.

A unitary hypothesis is offered to explain the various proliferative processes occurring around the phalanges. In the past, these have been separately designated as proliferative periostitis, bizarre parosteal osteochondromatous proliferation, and turret exostosis. Because the appearances of these entities depend on temporal factors, breaching of the periosteum, and local anatomic features, we suggest a single term, proliferative periosteal processes of phalanges.


Patellofemoral characteristics in patients with increased femoral anteversion.

In this study, the association between increased femoral anteversion and the characteristics of the patellofemoral joint was investigated in adults. In 17 female control patients, the anteversion angle of the femoral neck measured 12 degrees +/- 8 degrees and 11 degrees +/- 9 degrees for the right and left side, respectively. The sulcus angle of the patellofemoral joint was 145 degrees +/- 10 degrees and 146 degrees +/- 11 degrees, the congruence angle 7.2 degrees +/- 14 degrees and 7.8 degrees +/- 15 degrees, and the lateral patellofemoral angle 5.9 degrees +/- 6 degrees and 5.7 degrees +/- 6 degrees, respectively. In 15 female patients who were evaluated for clinical symptoms of increased femoral anteversion, the anteversion angle of the femoral neck was 30 degrees +/- 7 degrees and 31 degrees +/- 8 degrees degrees for the right and left side, respectively. The sulcus angle was 143 degrees +/- 8 degrees and 147 degrees +/- 9 degrees, the congruence angle 7.3 degrees +/- 12 degrees and 7.1 degrees +/- 13 degrees, and the lateral patellofemoral angle 6.4 degrees +/- 8 degrees and 6.1 degrees +/- 7 degrees, respectively. There was no correlation between the degree of femoral anteversion and the indices of the patellofemoral relationships. Thus, this study indicates that there is no association between increased femoral anteversion and abnormal patellofemoral characteristics.


Fracture-dislocation of the elbow with inferior radioulnar dislocation: a variant of the Essex-Lopresti injury.

We describe two patients with an Essex-Lopresti fracture dislocation in association with a dislocation of the elbow. This combination of injuries has not been previously reported. The Essex-Lopresti fracture is a rare injury, and the associated distal radioulnar dislocation is often missed. Meticulous radiographic evaluation of the wrist, including dynamic stress radiographs of the forearm, can lead to an earlier diagnosis and improved care of these patients.


Estrogen therapy for geriatric osteoporosis: just one ball in a complex juggling act.

The use of estrogens is the single therapy that has been found consistently to prevent bone loss and fractures in postmenopausal women. Traditional osteoporotic risk factors should be used to select women for bone densitometry. The numeric result provided by densitometry, combined with age-based comparisons, is extremely useful in convincing reluctant women to be treated. The few studies that have been done in geriatric women show that estrogen therapy continues to be effective in reducing bone loss, but the absolute benefit is less than in perimenopausal women. The effects of estrogen therapy extend beyond osteoporosis. A consensus of epidemiologic reports has shown that women who comply with postmenopausal estrogen therapy have a 30% to 50% reduction in the risk of coronary artery disease. Given the frequency of these two conditions, widespread use of estrogen as a national health care policy would be appropriate if it were not for the evidence that estrogens may increase the risk of breast cancer and endometrial cancer. Given these lingering cancer fears, recent calls for a randomized national women's health study of postmenopausal estrogen therapy should be heeded.


Role of calcium in preserving the skeletal health of aging women.

During the years from adolescence through senescence, the skeleton passes through identifiable phases: consolidation, maturity, menopause, and senescence. Skeletal dynamics and calcium requirements are different during each phase. A adult woman can avoid the skeletal deterioration caused by calcium deficiency if she maintains a minimum daily calcium intake of 800 mg. Increased calcium intake will not increase skeletal mass in mature, premenopausal women and will not prevent bone loss in postmenopausal women. Because intestinal absorption decreases with age, daily calcium intake of 1000 to 1200 mg is recommended for the elderly. Women can increase their dietary calcium intake in various ways, including increasing intake of dairy products, eating calcium-rich nondairy foods, purchasing foods fortified with calcium, and, if all other methods prove inadequate, using calcium supplements. Physicians must prescribe calcium only after learning what is needed for a particular woman's skeletal health by determining that woman's stage of skeletal development and approximate calcium intake; if intake is insufficient, it should be adjusted to the level appropriate at that stage.


Bisphosphonate therapy for postmenopausal osteoporosis.

Bisphosphonates are agents that are potentially useful for treatment of osteoporosis. They are antiresorptive agents, increasing bone mass by decreasing the frequency of osteoclast activation or the depth of osteoclast resorption, or both. Intermittent cyclical therapy with etidronate has been shown to be effective for postmenopausal osteoporosis in two controlled studies. Several second- and third- generation bisphosphonates are undergoing active clinical trials.


Fluorides and osteoporosis.

Sodium fluoride has clearly been shown to have pronounced effects on the skeleton, probably more than any other currently available therapeutic agent. Unfortunately, these effects appear to be both beneficial and potentially toxic at the same time. A more clear understanding is needed of the basic mechanisms whereby these effects (both beneficial and detrimental) are exerted. When such data are forthcoming, it may be possible to modify the therapeutic use of fluoride in osteoporosis and other brittle bone diseases such that the beneficial effects outweigh the toxic effects much more completely than is currently the case. Until such time, and despite thirty years of meaningful clinical investigation, we must conclude that sodium fluoride has no role in clinical medicine outside the confines of properly conducted clinical research studies.


Vitamin D metabolism and therapy in elderly subjects.

Serum 25-hydroxyvitamin D declines in elderly subjects. This decrease reflects, in part, a lower vitamin D intake. But changes in serum 25-hydroxyvitamin D are more marked in the northern latitudes of the world because less vitamin D synthesis occurs n the skin as a result of a reduced amount of ultraviolet light. Consequently, vitamin D deficiency leading to osteomalacia is more common in thr northern latitudes, particularly among the elderly. The Recommended Daily Allowance of 200 IU of vitamin D in the elderly may be insufficient, since higher doses of 800 IU/day have been shown to reduce the incidence of osteoporotic fractures. The use of more potent analogues of vitamin D, such as calcitriol (Rocaltrol), should be reserved only for those patients who have established vertebral osteoporosis and who generally have more pronounced malabsorption of calcium.


Glucocorticoid-induced osteoporosis.

The incidence of osteoporosis in patients receiving long-term glucocorticoid therapy is 30% to 50%. Trabecular bone is lost more rapidly than cortical. The cause of glucocorticoid-induced bone loss is multifactorial. Gastrointestinal absorption of calcium falls and urinary excretion rises, production of gonadal hormones decreases, and bone formation is inhibited in the presence of glucocorticoids. Bone loss can be minimized by using the lowest effective dose of a glucocorticoid with a short half-life, maintaining good nutritional status and physical activity, limiting sodium intake and giving a thiazide diuretic, maintaining serum 25-OHD at the upper limits of the normal range, giving estrogen replacement therapy to postmenopausal and amenorrheic women, and giving testosterone to men with low serum testosterone levels. The use of calcitonin or bisphosphonates should be considered.


Increased incidence of syphilis in Tennessee during the 1980s: challenges for a new decade.

Although recent increases in the incidence of syphilis are well known to public health officials, the general medical community is less well informed regarding the dramatic rise in cases. We present trend data from Nashville and Tennessee over the past decade. These statistics emphasize specific factors, such as drug abuse, that contribute to new difficulties in controlling this sexually transmitted disease.


Comparability of alcohol and drug use in injured drivers.

During a recent 5-month period, 201 injured drivers were admitted to a level 1 trauma center. Blood alcohol concentrations (BACs) and drug screens were obtained in 187 and 164 subjects, respectively. BACs were positive in 37% and other drugs were confirmed in 40%, suggesting that alcohol and drug use among injured drivers is comparable. More than half of the drivers using alcohol also had drugs detected on the screening examination. Other investigators have previously established driving impairments associated with some of these drugs. These results indicate that the drug problem on our highways may be greater than previously recognized.


Acute phenobarbital intoxication.

Phenobarbital is a long-acting barbiturate often prescribed for seizure disorders. It has a high abuse potential and was commonly used in suicide attempts in the past. Although benzodiazepines are now more frequently used in suicide attempts, barbiturate intoxications are still occasionally seen and constitute a medical emergency. The management of phenobarbital overdose includes cardiac and respiratory support, cathartics, activated charcoal, and alkaline diuresis. In severely compromised patients, hemodialysis and hemoperfusion can be used to enhance drug clearance.


Reconstruction of calvarial defects.

We subdivide the calvarium into three zones, each with its special reconstructive requirements. Based on our experience with calvarial defects in 13 patients, we favor use of autogenous material, especially in the face of previous infection or a scarred recipient bed. Alloplasts give excellent forehead contour but alloplastic reconstruction should be delayed for 1 year after injury. Vascularized bone grafts maintain contour well. They are best suited to large periorbital defects. At other locations we favor split calvarial free bone grafts. Occasionally, the defect may be so large as to warrant grafts from multiple donor sites. Use of vascularized muscle helps eradicate infection, provides a vascularized bed for free bone grafts, and fills dead space. The frontal sinus is managed either by cranialization (if the posterior wall is involved) or by mucosal stripping with obliteration of the nasofrontal duct. Additional technical considerations include rigid bone fixation, surgical exposure through a bicoronal incision, and meticulous handling of bone grafts.


Severe essential tremor compared with Parkinson's disease in male veterans: diagnostic characteristics, treatment, and psychosocial complications.

Essential tremor (ET), more common than Parkinson's disease (PD), has commonly been considered "benign." This investigation compared diagnostic characteristics, patient satisfaction with treatment, and psychosocial complications between a group of male patients treated for essential tremor and a group of male parkinsonian patients. Those who had ET tended to be more commonly misdiagnosed than those with PD. Fewer ET patients were satisfied with response to treatment than PD patients. Both groups equally expressed embarrassment about their condition, and both perceived similar difficulties with common activities of daily living and social situations. There were no significant differences between ET and PD patients for history of ethanol use or pharmacotherapy for anxiety or depression.


Hickman catheter malposition in central venous tributaries: an avoidable error?

We report three cases of erroneous positioning of Hickman catheters into central venous tributaries. The malposition was not diagnosed intraoperatively because of proximity of such veins to the superior vena cava. Suspicion of misplacement raised by early postoperative catheter malfunction should allow for correction by percutaneous vascular catheters.


Clinical management of postmenopausal osteoporosis.

Today, 24 million Americans are at risk for osteoporosis. Of the 2 million fractures that occur each year in the United States, approximately 1.3 million are directly due to osteoporosis. Osteoporosis, a preventable and treatable condition, takes on great importance because of the enormous impact these fractures can have on mortality, health care costs, patient productivity, independence, and self-esteem. Advances in diagnostic techniques and improved understanding of risk factors allow clinicians greater acumen in the classification and diagnosis of osteoporosis. Today, FDA-approved therapy for the treatment of postmenopausal osteoporosis includes calcium and vitamin D supplementation, estrogen and progesterone, and calcitonin-salmon. This article presents a review of the current understanding of each of these as well as experimental forms of therapy.


Physician-executives past, present, and future.

The dramatic changes in the United States' health care system during the last decade have sparked increasing interest in physician-executives. These executives, skilled in both clinical medicine and health care management, can be found in hospitals, managed care organizations, group practices, and government institutions. This paper outlines the physician-executive's roles and the development process. The remarkable growth in the number of physician-executives is expected to continue as they demonstrate their abilities to help health care providers expand ambulatory services, facilitate provider-physician relationships and physician recruitment, and lend expertise in quality improvement and risk management issues.


Raccoon heartworm causing a facial mass.

A Dirofilaria tenuis subcutaneous nodule was found in the supraorbital area of a 77-year-old woman living in Miami Beach. Removal of this nodule revealed the worm and confirmed the diagnosis. Infection with Dirofilaria tenuis is most common in southern Florida because of the high incidence of these worms in their natural hosts--raccoons and opossums.


Tension pneumothorax as a presentation of traumatic diaphragmatic hernia.

Spontaneous pneumothorax and tension pneumothorax are being increasingly recognized as complications of traumatic diaphragmatic hernia, particularly when presentation is delayed. This underscores the importance of suspecting the diagnosis of diaphragmatic hernia in patients with a recent or remote history of blunt or penetrating trauma to the chest or abdomen and an unusual or an atypical thoracic process. Once the diagnosis is suspected, confirmation with contrast studies, CT, or MRI should be obtained and surgical repair undertaken without delay.


Abdominal pain resulting from cerebrospinal fluid pseudocyst and cholelithiasis.

Patients treated with ventriculoperitoneal (VP) shunt procedures for hydrocephalus may have abdominal pain related to complications stemming from the shunt tubing itself or to other intra-abdominal disease. In patients with VP shunts, usually children, lack of absorption of cerebrospinal fluid (CSF) may produce a painful abdominal CSF pseudocyst. We have reported the rare occurrence of a CSF pseudocyst in an adult. The patient was also found to have cholelithiasis.


Severe hypertension associated with an intrarenal aneurysm.

A 26-year-old woman with regularly documented normal blood pressure had sudden onset of severe hypertension. Investigation revealed an intrarenal artery aneurysm involving the upper pole of the left kidney, as well as elevated levels of both renin and aldosterone. With ACE inhibitor therapy, blood pressure promptly returned to normal, and subsequent surgical removal of the upper pole of the involved kidney has resulted in normal blood pressure for 9 months of follow-up. Although uncommon, intrarenal aneurysms may lead to severe renal vascular hypertension that is relieved by surgery. This definitive procedure may not take place if one is not aware of the excellent response to ACE inhibitors in this situation.


Morphology of the dens. A quantitative study.

Morphometric studies of the dens of the second cervical vertebra were performed on a sample of one hundred twenty bones from the Hamann-Todd Collection. Data were collected on the longitudinal and transverse dimensions of the dens, as well as the size of the dens relative to the centrum of C2. Relationships of dens dimensions to body size and sexual dimorphism were evaluated. In both longitudinal and transverse mean dimensions, the dens in males was slightly, but significantly larger (5-10%) than in females. The relative distributions of dens dimensions were consistently skewed toward the higher values in males and the lower values in females. Body height or weight were not significantly correlated with dens dimensions, and were therefore poor predictors of the size of the dens. Implications for screw fixation of fractures of the dens are discussed.


The prevalence of cervical zygapophyseal joint pain. A first approximation.

A null hypothesis was tested to the effect that cervical zygapophyseal joint pain was uncommon. The prospectively recorded responses were reviewed of 318 consecutive patients with intractable neck pain who underwent provocation discography and cervical zygapophyseal joint blocks. Symptomatic zygapophyseal joints were encountered in 25% of the sample with a possibility that a further 38% suffered zygapophyseal pain but were not appropriately investigated. The null hypothesis was rejected. Cervical zygapophyseal joint pain is not rare, and is worthy of further consideration not just in research but in clinical practice.


Abnormal instantaneous axes of rotation in patients with neck pain.

Instantaneous axes of rotation for cervical motion segments C2-3 to C6-7 were determined in 109 patients with uncomplicated neck pain. Their location in each patient was compared to normal ranges determined in a previous study of 46 asymptomatic individuals. Unequivocally abnormal instantaneous axes of rotation were found in 46% of patients, and marginally abnormal instantaneous axes of rotation were found in a further 26% of patients. Abnormal instantaneous axes of rotation significantly correlated with the presence of neck pain, but the location of an abnormal axis did not correlate with the segmental source of pain as determined by provocation discography or zygapophyseal joint blocks.


Spinal mobility and posture in adolescent idiopathic scoliosis at three stages of curve magnitude.

Spinal posture and mobility were studied in 71 girls with progressive adolescent idiopathic thoracic scoliosis. Measurements were carried out by inclinometers and a compass in three planes; sagittal, frontal, and horizontal. The patients were divided into three groups according to the curve magnitude. Group 1 had curves smaller than 25 degrees, group 2 had curves between 25 and 35 degrees, and group 3 had curves greater than 35 degrees. The positional inclines of sacrum, upper lumbar and upper thoracic areas became more vertical as the curve size increased resulting in smaller lumbar lordosis and thoracic kyphosis. In the thoracic spine flexion and bending to the right was smaller in group 3 than in the other groups. Rotations in both clockwise and counterclockwise directions decreased as the curve size increased. In the lumbar spine only bending to the left decreased significantly with the curve size increase. All thoracic and lumbar movements except lumbar rotations had a general tendency to stiffening as the curve size increased. Of the mobility measurements thoracic rotation most clearly decreased with increased curves, which together with straightening of the spine can be important features in the pathomechanism of a progressive idiopathic thoracic curve.


Diurnal changes in the profile shape and range of motion of the back.

The diurnal height change reported to occur in young adults was investigated to characterize changes in the lumbar range of motion, spinal profile, and range of motion of the back. Twelve subjects aged 18-22 years were measured using stereophotography and standard clinical examinations in the evening and after a minimum of 8 hours of complete bed rest. The average increase in height was 20 mm. Forty percent of the height increase took place in the lumbar spine without change in the depth of the lordosis, and forty percent took place in the thoracic curve with a decrease in the kyphosis. The remaining 20% of the height increase was not located, but no measurements were taken of the cervical spine. Range of motion studies revealed that lumbar flexion, as measured using the lumbar flexion increment, was decreased in the morning, and straight leg raise was decreased when measured clinically but not when measured photographically. Extension, rotation, and femoral stretch test were not affected. The authors conclude that stereophotogrammetry offers an accurate, noninvasive way to study spinal profiles. Further work is needed to assess and quantify the relative motion of the skin and the underlying structures.


Morphologic and histochemical characteristics of skeletal muscle after long-term intramuscular electrical stimulation.

The purpose of this investigation was to examine the morphologic and histochemical characteristics of paraspinal muscles in patients with scoliosis after long-term electrical stimulation. Thirty-six children with idiopathic scoliosis, who had been treated with implantable muscle stimulators, had paraspinal muscle biopsies at the time of implantable muscle stimulator removal. Group A patients whose curve did not progress, had 2.9 years of stimulation stopped at skeletal maturity, with a further 1.5 years of nonstimulation before implant removal and biopsy. In group B patients, who had an average of 2.3 years of stimulation, the curve progressed and stimulation was continued until fusion and biopsy. Neither group showed any increase in the frequency of pathologic changes of paraspinal muscles contrasted with values reported in the literature for scoliotic muscle. In group A patients there was an increased proportion of type 1 fibers on the convex side of the curve compared to the concavity. Despite this finding the curves did not require fusion, suggesting that the increased percentage of type 1 fibers was not the cause of the scoliosis. In group B patients there was an even higher type 1 concentration on the convex side contrasted to the convex side of group A patients.


A comparative study of computed tomographic and plain radiographic methods to measure vertebral rotation in adolescent idiopathic scoliosis.

A comparative analysis of two methods of measuring vertebral rotation in adolescent idiopathic scoliosis is reported in this article. Nash and Moe's pedicle shift method (using plain anteroposterior radiographs) is compared with a new method using computed tomographic scans. The computed tomographic scans of the whole length of the major curve and the scout films obtained from seventeen girls aged 12.5-14 years were measured for rotation of each vertebra of the curve (total number of vertebrae measured by two methods = 173). This study has three interesting new findings: 1) Those vertebrae with Nash & Moe grade 0 had up to 11 degrees of vertebral rotation when measured using the computed tomographic method. Therefore, Nash & Moe's grade '0' is not a neutrally rotated vertebra; 2) For Nash & Moe grade 1 and 2, the computed tomographic method revealed statistically significantly greater rotation for lumbar vertebrae than thoracic vertebrae. There was a similar pattern for Nash & Moe grade 0 but these differences were not statistically significant; and 3) Simple formulae are reported to convert Nash & Moe's grades into angle of vertebral rotation as obtained by CT method separately for thoracic and lumbar vertebrae.


Changes in vertebral rotation after Harrington and Luque instrumentation for idiopathic scoliosis.

This study was carried out to analyze the three-dimensional and in particular the rotational correction obtained after spine instrumentation for idiopathic scoliosis. Preoperative and postoperative radiographs and computed tomographic scans with single axial cuts through each vertebral level were obtained for 14 patients: 4 Harrington, 7 Luque, and 3 Harrington-Luque. Rotation of vertebrae relative to the spinal axis and rotation between vertebrae (segmental rotation) were measured from computed tomographic scans of instrumented and uninstrumented segments. The derotation and changes occurring after surgery were calculated. Before operation, rotation was maximal at the apex, and close to 0 at the end vertebra; segmental rotation was greatest at the end of the curve, and minimal at the apex. After Harrington instrumentation the apical vertebrae showed a median derotation of 16%, after Luque instrumentation it was 12% and after Harrington-Luque instrumentation it was 13%. Segmental derotation did not uniformly occur. Major derotation was obtained at the end vertebrae and 39% of the total derotation occurred outside of the instrumented levels of the spine.


Mechanisms of curve progression following sublaminar (Luque) spinal instrumentation.

Fifty-two patients with Luque instrumentation were reviewed for spinal deformities. Forty-two patients were reviewed during 1 year (longest 7.2 years) at follow-up. Two patients were included who lost correction within 1 year (both 8 months). Follow up averaged 2.9 years. Curve causes primarily were neuromuscular but included one was caused by idiopathic scoliosis, four by Scheuermann's disease, and 1 by post-laminectomy kyphosis. The Cobb angle progressed in 45% of patients postoperatively. Factors contributing to progression included progressive vertebral rotation or the crankshaft phenomenon (11), wire pull out (7), progressive pelvic obliquity (4), rod bending (3), pseudarthrosis (2), and rod migration (2). Factors correlating with progression were kyphosis, postoperative curve greater than 35 degrees, preoperative curve greater than 60 degrees, and not fusing to the pelvis in nonambulators. Crankshaft was common in patients Risser II or less but did not occur in more mature patients.


Iliac crest versus spinous process grafts in posttraumatic spinal fusions.

Results of posttraumatic spine fusions in 34 patients who had autogenous iliac crest grafts were compared with those of 70 patients who had autogenous spinous process grafts. The two groups of patients were otherwise homogenous, and fusion occurred in 32 (94%) of the iliac crest graft patients and 70 (100%) spinous process graft patients. However, average operative time (225 vs. 200 minutes) and operative blood loss (1371 vs. 1136 cc) were significantly higher in iliac crest graft patients (P less than 0.05), and five iliac crest graft patients had significant donor site complications. Use of spinous process grafts eliminated donor site problems, reduced operative time and blood loss, and produced a rate of arthrodesis equal to that of iliac crest grafts.