[A prospective two-year follow-up of thoracic and lumbar osteolytic vertebral fractures caused by multiple myeloma treated with balloon kyphoplasty]. / Zwei Jahre prospektive Nachuntersuchung von thorakalen und lumbalen osteolytischen Wirbelkörperfrakturen in Patienten mit einem multiplen Myelom--behandelt mittels Ballon-Kyphoplastie.

PURPOSE: Balloon kyphoplasty is a minimally invasive procedure for the stabilization of osteoporotic and osteolytic vertebral fractures. The purpose of this prospective study was to evaluate this operative procedure in the treatment of osteolytic vertebral fractures with regard to the reduction of pain and functional improvement of the patients and further to evaluate the restoration of vertebral height postoperatively. MATERIALS AND METHODS: In this study 26 patients (21 male, 5 female) with osteolytic vertebral fractures were treated with balloon kyphoplasty. In total, 59 vertebral fractures were treated with balloon kyphoplasty. Preoperatively conventional radiographs in lateral and a. p. views, CT and/or MRI were preformed. Pre- and postoperatively the clinical parameters using VAS (visual analogue scale) and the Oswestry score were evaluated. Radiographic scans were performed pre- and postoperatively and after 3, 6, 12 and 24 months. The vertebral height and endplate angles were measured. RESULTS: The median pain scores (VAS) decreased from pre- to post-treatment significantly (p < 0.05) as also did the Oswestry score (p < 0.05). Balloon kyphoplasty led to a significant and sustained reduction of pain resulting in a significant functional improvement for the patients. A significant restoration of vertebral height and reduction of the kyphotic angle could be achieved with the balloon technique (p < 0.05). Furthermore, the minimal-invasive procedure was able to stabilize the spine also over a longer period of 24 months. A radiation therapy and/or chemotherapy could be performed without loss of time. CONCLUSION: In the treatment of osteolytic vertebral fractures balloon kyphoplasty led to a quick and sustained reduction of pain and as well as a functional improvement for the patients. A restoration of the vertebral height and reduction of the kyphotic angle was especially attributable to the balloon technique. The balloon kyphoplasty was able to stabilize the fractured vertebrae in the long-term and was able to prevent an increase of kyphotic deformity. Balloon kyphoplasty is an outstanding alternative in comparison to the established therapeutic concepts in the treatment of osteolytic vertebral fractures.

Balloon kyphoplasty for the treatment of pathological fractures in the thoracic and lumbar spine caused by metastasis: one-year follow-up.

PURPOSE: To evaluate the clinical and radiographic outcomes of balloon kyphoplasty in patients with fractures of the thoracic and lumbar spine caused by metastatic disease. MATERIAL AND METHODS: 64 balloon kyphoplasty procedures were performed in 31 patients (18 females and 13 males with bone metastasis), 28 of whom were followed up over a period of 1 year. Symptomatic levels were identified by clinical presentation, magnetic resonance imaging (MRI), radiographs, and computed tomography (CT). In the prospective 1-year follow-up, visual analog scale (VAS) and Oswestry Disability Score were documented. Radiographs were performed pre- and postoperatively, and at 3, 6, and 12 months. Vertebral height and kyphotic deformity were measured to assess restoration of the sagittal alignment. RESULTS: The median pain scores (VAS) decreased significantly (P<0.05) from pre- to post-treatment, as did the Oswestry Disability Score (P<0.05). Polymethyl methacrylate (PMMA) cement leakage was detected in eight of 64 vertebral bodies (12.5%), but did not have any clinical relevance. During 1-year follow-up, balloon kyphoplasty stabilized vertebral height and prevented further kyphotic deformity. CONCLUSION: Balloon kyphoplasty is an effective, minimally invasive procedure for the stabilization of pathological vertebral fractures caused by osteolytic lesions of vertebral bodies due to metastatic disease. It gives a statistically significant reduction of pain and prevents further kyphotic deformity of the spine.

Incidence of adjacent vertebral fractures in patients treated with balloon kyphoplasty: two years' prospective follow-up.

PURPOSE: To evaluate the long-term outcomes of 37 patients with 60 osteoporotic vertebral fractures, located in the thoracic and lumbar spine, treated with balloon kyphoplasty. MATERIAL AND METHODS: Fourty-two patients (15 males and 27 females) with 67 osteoporotic vertebral fractures were treated with balloon kyphoplasty. We were able to have 2-year follow-up of 37 patients with 60 treated vertebrae. Baseline fracture rate in these 37 patients was 1.9 (60 fresh fractures and 11 old fractures already healed). Symptomatic levels were identified by correlating the clinical presentation with conventional radiographs, computed tomography (CT), and/or magnetic resonance imaging (MRI). During the 2-year follow-up, reduction in pain was determined. The effects on pain symptoms were measured on a self-reported visual analog scale (VAS) and the Oswestry score was documented to assess disability. Radiographic scans were performed pre- and postoperatively, and after 3, 6, 12, and 24 months. The vertebral height and endplate angles were measured to assess the restoration of the sagittal alignment. RESULTS: The median pain scores (VAS) decreased significantly from pre- to post-treatment as did the Oswestry Disability Score (P<0.05). This improvement was maintained at 2-year follow-up. In eight patients (21.6%) (five female, three male), an adjacent fracture occurred in 11 vertebrae (18.3%) within 3 weeks to 22 months of follow-up (after 22 months no adjacent fracture occurred). This makes an annualized refracture rate of 10% (18.3/22 x 12). In three patients the adjacent fractures were asymptomatic. Five patients with symptomatic adjacent fractures (eight vertebrae) wanted to be treated again with balloon kyphoplasty. Clinically asymptomatic cement leakage occurred in nine of 67 vertebral bodies (13.4%). During 2-year follow-up, this surgical technique demonstrated restoration and stabilization of the height of the vertebral body. CONCLUSION: Balloon kyphoplasty is an effective, minimally invasive procedure for the stabilization of osteoporotic vertebral fractures, leading to a statistically significant reduction of pain status.

Percutaneous balloon kyphoplasty in the treatment of pathological vertebral body fracture and deformity in multiple myeloma: a one-year follow-up.

PURPOSE: To evaluate the clinical and radiographic outcomes of balloon kyphoplasty in patients with fractures of the thoracic and lumbar spine caused by multiple myeloma. MATERIAL AND METHODS: Vertebral fractures due to multiple myeloma were treated by balloon kyphoplasty (20 patients, 48 vertebral bodies). Symptomatic levels were identified by clinical presentation, magnetic resonance imaging (MRI), radiographs, and computed tomography (CT). During the following year, visual analog scale (VAS) and Oswestry disability score were documented. Radiographs were taken pre- and postoperatively at 3, 6, and 12 months. Vertebral height and kyphotic deformity were measured to assess restoration of the sagittal alignment. RESULTS: The median pain scores (VAS) decreased significantly from pre- to posttreatment, as did the Oswestry disability score (p < 0.05). Clinically asymptomatic cement leakage occurred at 5 fracture levels (10.4%). During 1-year follow-up, this surgical technique demonstrated restoration and stabilization of the height of the vertebral body. CONCLUSION: Balloon kyphoplasty is an effective minimally invasive procedure for stabilizing pathological vertebral fractures caused by multiple myeloma and leading to a statistically significant reduction of pain status. Balloon kyphoplasty stabilizes the vertebral body height, but is only partially able to prevent further kyphotic deformities.

[Computed tomographic criteria as expected effect to inhaled nitric oxide in patients with severe acute respiratory distress syndrome]. / Computertomographische Kriterien für den zu erwartenden Effekt von inhaliertem Stickstoffmonoxid bei Patienten mit schwerem akutem Lungenversagen.

PURPOSE: Inhaled nitric oxide (iNO) is an effective therapy for severe hypoxemia in most patients with acute respiratory distress syndrome (ARDS). For unknown reason, a subset of ARDS patients does not respond favorably to iNO therapy. We hypothesized that radiological manifestation of lung injury may be related to iNO response. MATERIALS AND METHODS: We retrospectively analyzed data from n = 25 ARDS patients who received iNO, and underwent chest CT within 72 h prior to inhaled treatment. The morphology of coherently pathologic lung tissue was characterized by the length of the borderline between consolidated, infiltrated and atelectatic lung tissue and radiologically normal lung tissue. This quantity was expressed as relative fraction of the visceral pleural circumference and averaged over all CT slices. Furthermore we semiquantitatively determined the total volume of consolidated lung tissue as part of the whole lung. RESULTS: In n = 6 non-responders to iNO (DeltaPaO2 < 10 %), we determined a short relative borderline between normal and consolidated lung tissue due to the presence of large and coherently consolidated lung regions. In n = 19 iNO responders (DeltaPaO2 > 10 %), we found significantly less coherently consolidated lung tissue evidenced by an increased relative borderline when compared to iNO non-responders (0.09 +/- 0.02 vs. 0.1 +/- 0.01; P < 0.05). Moreover, there was a moderate and significant correlation between DeltaPaO2 induced by iNO and the relative borderline in all patients studied (R = 0.59; P < 0.05). Total fraction of consolidated lung tissue volume was not different between iNO non-responders and responders (60 +/- 3 % vs. 54 +/- 2 % n. s.). CONCLUSION: Our data demonstrate that the gross morphological distribution of pathological lung tissue influences iNO response in ARDS. Inhaled NO was most beneficial in injured lungs characterized by many small consolidated areas surrounded by normal lung tissue. The increased borderline between pathologic and normal lung tissue offers additional possibility for iNO to divert blood flow from shunt areas to ventilated lung regions, which consequently improves arterial oxygenation.

[Accuracy of CT-based navitation of pedicle screws in the thoracic spine compared with conventional technique]. / Genauigkeit der CT-basierten Navigation von Pedikelschrauben an der Brustwirbelsäule im Vergleich zur konventionellen Technik.

The goal of this study was to evaluate the accuracy of CT-based computer-assisted pedicle screw insertion in the thoracic spine in patients with fractures, metastases, and spondylodiscitis compared to a conventional technique. A total of 324 pedicle screws were inserted in the thoracic spines of 85 patients: 211 screws were placed using a CT-based optoelectronic navigation system assisted by an image intensifier and 113 screws were placed with a conventional technique. Screw positions were evaluated with postoperative CT scans by an independent radiologist. In the computer-assisted group, 174 (82.5%) screws were found completely within their pedicles compared with 77 (68.1%) correctly placed screws in the conventional group ( p<0.003). Despite use of the navigation system, 1.9% of the computer-assisted screws perforated the pedicle wall by more than 4 mm. The additional use of the image intensifier helped to identify the correct vertebral body and avoided cranial or caudal pedicle wall perforations.

Unknown AV-fistula as reason for post-traumatic hematoma of the thigh.

A case is reported of a 28-year-old patient with gradually developing massive swelling of the right thigh after sustaining a blunt trauma. 3 1/2 months after the injury, surgery was performed because of a persisting tumor at the thigh. Intraoperatively, massive bleeding occurred, the bleeding vessel was sutured. Postoperative angiography disclosed arteriovenous (av) fistulae from the internal iliacal artery to a gluteal vein as source for the bleeding. The feeding artery was closed by coiling, the patient recovered completely. To the authors' knowledge, development of an av-fistula following blunt trauma has not been described previously. Similarly, the differential diagnosis of a posttraumatic bleeding of a congenital av-malformation was not yet reported. The authors emphasize, that prior to the surgery of inadequately behaving hematomas, an angiography should be performed.

Tumor vascularization in experimental melanomas: correlation between unenhanced and contrast enhanced power Doppler imaging and histological grading.

The purpose of this study was to evaluate the reliability of unenhanced and enhanced power Doppler sonography in visualization of intratumoral angioneogenesis. Thirty-seven malignant melanomas, which had been implanted intra- or subcutaneously in 22 mice, were examined. Various B-mode criteria, power Doppler criteria and spectral Doppler parameters were evaluated before and after IV-application of the d-galactose-based contrast agent Levovist. After sonographic examination, all tumors were analyzed histologically with semiquantitative grading of tumoral vascularization. Unenhanced, in 70% of the tumors, no intratumoral vessels were visible using power Doppler, but only in 11% of the intracutaneous and in 0% of the subcutaneous after injection of the contrast agent. The enhanced mode was definitely superior to unenhanced Doppler in showing the intratumoral vascularity. The intratumoral vascular structure could be sufficiently analyzed in 30% of all tumors by unenhanced Doppler, but in 92% enhanced. The mean percentage vessel area increased about 433% after application of Levovist (intracutaneous: 485%, subcutaneous: 280%). Despite the missing direct correlation between the sonographically and histologically determined grade of tumor vascularization (Pearson's correlation unenhanced 0,356, p <.05/enhanced 0.395, p <.05), the correlation between the percentage vessel area and the histologic grade of vascularization was improved after application of the contrast agent (Pearson's correlation unenhanced 0.347, p <.05/enhanced 0.686, p <.01). We did not find a significant direct correlation between histologically and sonographically determined degree of vascularization. However, the correlation was improved using a d-galactose-based signal-enhancing agent in power Doppler sonography.

Vascularization of reactively enlarged lymph nodes analyzed by color duplex sonography.

PURPOSE: This study involved a prospective evaluation of the reliability of sonography, and especially duplex sonography, in confirmation of the benign nature of enlarged cervical lymph nodes. PATIENTS AND METHODS: In 53 untreated patients with enlarged cervical lymph nodes, B-mode, plain, and d-galactose-enhanced color duplex sonography were performed. The B-mode sonomorphology was analyzed for the structure of vascularization. Quantitative parameters such as maximum flow velocity, pulsatility index, and resistive index were also assessed. The benignity of the lymph nodes was confirmed by microscopic analysis. RESULTS: The B-mode showed 20 homogeneous lymph nodes, 23 with a central echogenoic line covering less than one third, and 10 with a distinct hilus sign extending to more than one third of the lymph node diameter. Microscopically, the least fibrotic or chronic inflammatory changes in the parenchyma were observed in the homogeneous lymph nodes, whereas those with central echogeneoity had fibrotic and lipoid hilus changes. Histologically, all lymph nodes had normal afferent and efferent hilus vessels. In 37 lymph nodes, the vessel structure could be reliably visualized by both plain and enhanced color duplex sonography, whereas in 16 it could only be demonstrated after the use of signal enhancement. Nine of 53 lymph nodes had Solbiati-(L/T-) indices below 2, which were suggestive of malignancy. Quantitative flow parameters did not provide useful information. CONCLUSION: Color duplex analysis of enlarged lymph nodes is a useful method for assessment of benignity, especially after application of a signal-enhancing agent.

[Mn-TPPS4 in the diagnosis of malignant skin tumors. In vivo studies with high resolution magnetic resonance tomography in melanotic melanoma]. / Mn-TPPS4 in der Diagnostik von malignen Hauttumoren. In-vivo-Untersuchungen mittels hochauflösender Magnetresonanztomographie an melanotischen Melanomen.

PURPOSE: Some authors postulate an avidity of certain porphyrin derivatives for tumors. The aim of this study was to examine the contrast enhancement of implanted melanotic melanoma after application of Mn-TPPS4 to achieve a better characterization of this malignant skin tumor. MATERIAL AND METHOD: High-resolution MR imaging (2.0 Tesla, 2.0-cm surface-coil, T1-weighted FLASH-2D-sequence) was performed on 15 mice (C57b16) with intracutaneous implanted melanoma (B16F1), before and after intravenous administration of either Gd-DTPA (Magnevist, Schering, Berlin) as a reference contrast medium, or Mn-TPPS4 (Porphyrin Products, Schering, Berlin). The images were evaluated quantitatively by calculating percentage enhancement, slope of signal intensity-to-time curves, percentage increase of the signal intensity, signal-to-noise and contrast-to-noise-ratios. The qualitative evaluation was accomplished by visual assessment of the enhancement, the demarcation of the tumors from the surrounding tissue and the homogeneity of the tumors. RESULTS: Contrast medium-enhanced images showed an increased signal intensity from all tumors with no signifikant difference between the contrast media. Demarcation of tumors from the surrounding tissue was better following administration of contrast media; regressive and altered areas was more clearly depicted. CONCLUSION: A specific accumulation of the metalloporphyrin Mn-TPPS4 in melanotic melanoma could not be proved. Based on the small and insignifikant differences in the results obtained with the two contrast media, and on the side effects of the metalloporphyrin, the usefulness of Mn-TPPS4 as a contrast medium for MRT is limited.

D-galactose-based signal-enhanced color Doppler sonography of breast tumors and tumorlike lesions.

RATIONALE AND OBJECTIVES: This study sought to evaluate prospectively the diagnostic potential of unenhanced and enhanced color Doppler and power Doppler for the differentiation of tumors and tumorlike lesions of the breast. METHODS: Ninety-two patients with 110 tumors or tumorlike lesions of the breast were investigated by unenhanced and enhanced color and power Doppler ultrasound. The sonomorphologic aspects of vascularization were analyzed. In addition, maximal systolic frequency shift, resistance, and pulsatility indices were determined. RESULTS: In 15 (24%) of 63 primary carcinomas, 15 (68%) of 22 fibroadenomas, and all (100%) of 14 postoperative lesions, the sonomorphologic analysis for the differential diagnosis of breast tumors was improved after contrast enhancement in color Doppler mode. In comparing unenhanced color Doppler to power Doppler, the latter was found to be slightly superior (sensitivity, 60% vs. 67%; specificity, 39% vs. 45%, respectively); after enhancement, both modes were equivalent (sensitivity, 100% vs. 100%; specificity, 95% vs. 95%, respectively). Signal enhancement resulted in a significant improvement in sensitivity and specificity (P < 0.01). Typical signs of malignancy were irregular vessel calibers, serpiginous courses, penetration of the tumor's margin, and irregular reticular vascularization. The quantitative parameters proved not to be helpful for the differential diagnosis of breast tumors. CONCLUSIONS: By improved analysis of the vascularization pattern, d-galactose-enhanced color Doppler sonography was found to provide more reliable differential diagnostic information than unenhanced Doppler ultrasound in tumors and tumorlike lesions of the breast.

Cholesterol and sphingolipid enhance the Triton X-100 insolubility of glycosylphosphatidylinositol-anchored proteins by promoting the formation of detergent-insoluble ordered membrane domains.

Glycosylphosphatidylinositol (GPI)-anchored proteins can be isolated from both cells and sphingolipid and cholesterol-rich liposomes (SCRLs) in association with detergent-insoluble membranes. We found previously that detergent insolubility of lipids was characteristic of phases in which lipid acyl chains are ordered. We presented evidence that GPI-anchored proteins are insoluble because they associate with cholesterol and sphingolipid-rich lipid domains with properties similar to the liquid-ordered phase. Here, this model was tested by a variety of approaches. First, we demonstrated that saponin, which removes cholesterol from cell membranes and allows solubilization of GPI-anchored proteins by Triton X-100, had the same effect on the GPI-anchored protein alkaline phosphatase (PLAP) in SCRLs of appropriate lipid composition. The similarity of saponin action in cells and simple liposomes suggests that the compound disrupts protein-lipid interactions. However, direct interactions between PLAP and cholesterol were not needed for insolubility, because the protein was also insoluble in cholesterol-free liposomes containing lipid in an ordered phase. Instead, cholesterol acted by greatly enhancing the formation of a detergent-insoluble phase by sphingolipids, which have a tendency to form ordered phases. We propose that saponin solubilizes GPI-anchored proteins because the lipid composition of cell membranes (and the SCRLs used above) supports ordered phase formation in the presence but not the absence of cholesterol. Supporting this model, saponin did not promote Triton X-100 solubilization of PLAP in SCRLs with sphingolipid levels high enough to allow ordered phase formation in the absence of cholesterol. We also showed that two additional GPI-anchored proteins are detergent-insoluble in SCRLs and that detergent does not artifactually create ordered domains or cause components of solubilized membranes to associate with detergent-resistant membranes present in separate bilayers in the same lysate. We conclude that the ordered domain model explains the behavior of detergent-resistant membranes in liposomes and cells.

Effect of high pressure on the optical detection of gas by index-of-refraction methods.

An optical method for the detection of gas in high-pressure flow streams has been developed. One can detect gas by measuring the variation in intensity of reflected, p-polarized light at a sapphire-flow stream interface over a range of angles including the Brewster and critical angles for gas. The effects of high pressure and gas identity have been determined for this gas detection method. Pressure ranges to 20,000 psi of helium, nitrogen, argon, and methane along with a gas mixture were used in these experiments. Excellent agreement is obtained in the pressure- and gas-dependent shifts in critical angle between experimental observations and predictions based on literature values of gas densities and molar refractivities. Significant gas nonidealities are discussed in terms of the correspondence principle.

Left ventricular hypertrophy regression during antihypertensive treatment.

For more than 20 years hypertrophy regression has been in the focus of hypertension research. Many studies in animals have shown impressive reduction of left ventricular hypertrophy after medical treatment of hypertension. The most important result seems to be that hypertrophy can be almost completely reversed in young animals, whereas in older animals regression of left ventricular hypertrophy appears to be less complete. Hypertrophy regression in man seems much more difficult to prove. The direct correlation between left ventricular muscle mass and ECG changes has been disappointing in many studies. Echocardiography is able to show a comparatively good impression of left ventricular muscle mass and therefore can also demonstrate regression of left ventricular hypertrophy within its methodological limits. There is no doubt that today magnetic resonance imaging has by far the best imaging quality of all the clinical methods and is able to demonstrate both hypertrophy and its regression with incomparable accuracy. In the present clinical study hypertrophy regression has been demonstrated after 6 months of treatment with Carvedilol.

Regression of left ventricular hypertrophy.

Since our first studies on hypertrophy regression, this parameter has achieved an increasing interest in the treatment of hypertension. During the past 8 years we studied different groups of antihypertensive drugs with the use of magnetic resonance imaging (MRI). This article discusses the antihypertensive drug carvedilol. We examined 17 patients with diastolic blood pressure of at least 95 mm Hg and left ventricular wall thickness of at least 15 mm. Measurements were carried out before and after treatment with 25 mg/day carvedilol for 6 months. We demonstrated a significant regression of septal thickness from 17.7 to 16.3 mm. At each wall, three measurements at different points were performed by MRI and the means were calculated. Left ventricular ejection fraction and wall motion did not show any significant changes in radionuclide ventriculography after treatment. The diastolic blood pressure was reduced from 98.0 to 88.7 mm Hg. All differences are significant (p less than 0.05). There was no significant correlation between the extent of regression of septal hypertrophy and the degree of pretherapeutic hypertrophy, the age of patients, or the dimension of blood pressure reduction.

Roles of plasma clearance and corticosteroid-binding globulin in the developmental increase in circulating corticosterone in infant rats.

The aim of this study was to determine the role of plasma clearance in the developmental increase in plasma corticosterone concentration in the infant rat. Previous studies indicated that the corticosterone rise may be mediated entirely by a decrease in the MCR. The rationale of the current study was that if this is true, then corticosterone from an exogenous source (at a constant dose) should also produce a developmental increase in circulating levels of the hormone. Therefore, infant rats, aged 12, 16, and 21 days (i.e. near the beginning, middle, and end of the endogenous corticosterone developmental rise), were adrenalectomized and provided with a constant dose of corticosterone via sc pellets. There was a significant age-related increase in plasma corticosterone in pellet-treated pups which closely paralleled that seen in sham-operated littermates. This indicates that the decrease in plasma clearance is sufficient to account entirely for the normal developmental rise in plasma corticosterone. The declining MCR for corticosterone with increasing age is due primarily to a decrease in the apparent volume of distribution (Vd), which, in turn, may result from the concurrent increase in plasma corticosteroid-binding globulin (CBG). To investigate this possibility, the Vd of dexamethasone, a synthetic glucocorticoid that does not bind to CBG, was determined and compared with that of corticosterone. While the Vd of corticosterone declined significantly with age, there was no consistent change in the Vd of dexamethasone. Taken together, these data indicate that the decrease in clearance of corticosterone from plasma with increasing age is sufficient to account for the normal developmental rise of corticosterone. Moreover, increased binding of corticosterone to CBG appears to be responsible for decreases in Vd and clearance.

Lead in house dust of Christchurch, New Zealand: sampling, levels and sources.

Lead in house dust was determined in different areas of Christchurch, New Zealand. The mean lead level in newer (post-1950) areas of the city was 460 micrograms g-1, whereas in older (pre-1950) areas it was 830 micrograms g-1. These levels also relate to the type of building material (brick or wood, respectively) and type of paint used (non-lead or lead paint, respectively). For the newer areas of the city, it was estimated that approximately 90% of the lead was derived from petrol additives (via street dust and aerosol), whereas in the older areas, approximately 50% of the lead was estimated to come from petrol lead and 45% from paint lead.

Q fever in Los Angeles County. Serological survey of human and bovine populations.

Q fever is endemic and enzootic in Los Angeles County. A serological survey conducted in 1949 is compared with a current survey. Infection in dairy herds is now almost universal, while the prevalence of positive complement fixation titers in man only increased from 1.2 percent to 2.3 percent (p <0.10). The relative stability in man is accounted for by the increase in temperature requirements for milk pasteurization, the decrease in consumption of raw milk and the decrease in the number of dairy farm foci.