First bilateral lobar lung transplant in Ireland: advanced operative strategies in lung transplantation.

Lobar lung transplantation is an option that provides the possibility of transplantation of small size recipients with size-mismatch donor lungs by surgically reducing the size of donor lungs. We report our first experience of bilateral lobar lung transplantation of big donor lungs, in a small size urgently listed recipient, after size reduction. A 24 years old girl with end stage cystic fibrosis received the bilateral lobar lung transplant. She made very good recovery postoperatively and was discharged home two weeks following surgery.

Superior sensitivity and decreased time to detection with the Bactec Peds Plus/F system compared to the BacT/Alert Pediatric FAN blood culture system.

Here, we compare the sensitivities and times to detection (TTD) of BacT/Alert Pediatric FAN (PF) and Bactec Peds Plus blood culture bottles. Test bottles were inoculated with 2 ml of banked whole blood, 1-ml aliquots of antibiotic suspension, and organisms diluted to simulate a bacteremia level of 10 to 100 CFU/ml. The control bottles were inoculated with 3 ml of banked blood and organism suspensions only. The organism-drug combinations were Staphylococcus epidermidis and vancomycin, methicillin-resistant Staphylococcus aureus and vancomycin, Streptococcus pneumoniae, vancomycin, and ceftriaxone, Streptococcus agalactiae, ampicillin, and cefotaxime, Escherichia coli, cefotaxime, and cefepime, Pseudomonas aeruginosa, piperacillin-tazobactam, cefepime, and gentamicin, Neisseria meningitidis and ceftriaxone, and Haemophilus influenzae and ceftriaxone. The control and test bottle combinations were tested in duplicate. The bottles were incubated for 5 days; 32 control and 104 test bottles were incubated. Overall, the bacterial recovery rates for the PF and Peds Plus bottles were 37% and 62%, 94% and 100% in the controls, 19% and 50% in the test bottles, and 33% and 92% in the bottles with vancomycin, respectively. No bacteria were recovered from the bottles with S. pneumoniae, S. agalactiae, E. coli, N. meningitidis, or H. influenzae in combination with cefotaxime or ceftriaxone. The Peds Plus system detected P. aeruginosa in bottles with cefepime and piperacillin-tazobactam, but the PF system recovered bacteria only in bottles with trough levels of piperacillin-tazobactam. The mean TTD were shorter in the Peds Plus system controls (14.2 versus 18.0 h; P = 0.001) and the test bottles (14.3 versus 17.8 h; P = 0.008) than in the PF bottles. Overall, we demonstrated superior sensitivity, TTD, and antibiotic neutralization in the Bactec Peds Plus system compared to those in the Pediatric FAN system.

Frequency of respiratory symptoms among rice mill workers in Bangladesh: A cross-sectional study.

Background and Aims: Rice mill workers are frequently exposed to rice dust specks containing bacteria, endotoxins, spores, and chemicals in workplaces. Consequently, they develop diverse respiratory symptoms that lead to increased disability and social burden. The present study was conducted to observe the frequency of respiratory symptoms among rice mill workers in Bangladesh. Methods: This cross-sectional study was conducted at different rice mills in Rangpur district of Bangladesh. Three hundred and forty-six rice mill workers, both male and female of 18 years and above, with a job experience of at least 3 years, were selected as study subjects. An equal number of people who had never worked at rice mills were selected from the nearby locality as the nonexposed group. Enquiries were made regarding respiratory symptoms with the help of a preformed questionnaire which contained sociodemographic characteristics, occupational history, potential confounding factors, and physical parameters. A respiratory dust sampler was used to measure workplace dust concentration. Results: The presence of one or more respiratory symptoms was significantly higher among rice mill workers than in the nonexposed group (52.3% vs. 17.6%). Rice mill workers who worked for more than 10 h and had a working experience of more than 15 years had a higher frequency of respiratory symptoms (41.3% and 39.8%, respectively). Rice mill workers with body mass index (BMI) <18.5 also exhibited more respiratory symptoms (25.4%). All working sections had a higher-than-average dust concentration level, with the milling section being the dustiest (PM 2.5 492.1 µg/m3). Conclusion: This study showed an increased frequency of respiratory symptoms among rice mill workers of Bangladesh. Longer working experience and working hours, low BMI and high dust concentration levels were strongly associated with that increase in frequency.

Single coronary artery; extremely rare coronary anomaly successfully treated surgically in young adult male.

Single coronary artery arising from aortic root, is a rare congenital anomaly. A 30-year-old male presented with acute myocardial infarction (MI) complaining of chest pain and raised troponin levels. Emergency angiography showed no coronary lesions but both left and right coronary arteries arising from single ostium. Patient was operated electively and perioperative findings confirmed the diagnosis of single coronary artery, as left coronary artery after taking origin from right sinus of valsalva runs through the septum, before dividing into left anterior descending and circumflex branches. The single coronary ostium opened with a slit like incision over the course of left main coronary, making the size of ostium three to four times bigger than the native one. In addition left internal mammary artery was harvested and grafted to the left anterior descending branch distally. Patient made successful recovery. Four months follow up dobutamine stress echo showed no inducible ischemia.

Interinstitutional and intrainstitutional transmission of a strain of Acinetobacter baumannii detected by molecular analysis: comparison of pulsed-field gel electrophoresis and repetitive sequence-based polymerase chain reaction.

Pulsed-field gel electrophoresis and repetitive sequence-based polymerase chain reaction provided comparable strain discrimination with minor discordance in typing Acinetobacter baumannii clinical isolates from patients at our hospital and affiliated institutions. Typing revealed a cluster strain with intrainstitutional and interinstitutional spread during the study period. A long-term acute care facility may have been the reservoir.

Transdermal administration of clonidine for treatment of high BP.

The effectiveness of transdermally administered clonidine hydrochloride was evaluated in a multicenter study in 85 patients with mild essential hypertension. The drug was incorporated into small self-adhesive delivery systems (pliable skin patches, 3.5-sq-cm area) designed to continuously deliver 0.1 mg of clonidine hydrochloride per day. These devices were changed by the patients themselves at weekly intervals. Diastolic BP fell by at least 10% in 37 patients and was normalized (less than 90 mm Hg) in 54 patients (64%); 17 of these responding patients required only one skin patch, 27 required two, and the other ten responders required three. The antihypertensive action of the transdermal clonidine was sustained for the full three months of study. Side effects were similar to those during conventional oral treatment, but appeared to be milder.

Fabry disease mimicking multiple sclerosis: Lessons from two case reports.

Fabry disease is an X-linked lysosomal storage disorder that can mimic multiple sclerosis. We present two cases of heterozygous adult women where clinical and radiological features initially suggested a diagnosis of multiple sclerosis. This led us to review the early clinical course and neurological features of Fabry disease and highlight the importance of assessing non-neurologic (systemic) symptoms when considering a diagnosis of multiple sclerosis and the need for specialist interpretation of neuroradiological findings.

Nitric oxide mediates cerebral ischemic tolerance in a neonatal rat model of hypoxic preconditioning.

Neuroprotection against cerebral ischemia can be realized if the brain is preconditioned by previous exposure to a brief period of sublethal ischemia. The present study was undertaken to test the hypothesis that nitric oxide (NO) produced from the neuronal isoform of NO synthase (NOS) serves as a necessary signal for establishing an ischemia-tolerant state in brain. A newborn rat model of hypoxic preconditioning was used, wherein exposure to sublethal hypoxia (8% oxygen) for 3 hours renders postnatal day (PND) 6 animals completely resistant to a cerebral hypoxic-ischemic insult imposed 24 hours later. Postnatal day 6 animals were treated 0.5 hour before preconditioning hypoxia with the nonselective NOS inhibitor L-nitroarginine (2 mg/kg intraperitoneally). This treatment, which resulted in a 67 to 81% inhibition of calcium-dependent constitutive NOS activity 0.5 to 3.5 hours after its administration, completely blocked preconditioning-induced protection. However, administration of the neuronal NOS inhibitor 7-nitroindazole (40 mg/kg intraperitoneally) before preconditioning hypoxia, which decreased constitutive brain NOS activity by 58 to 81%, was without effect on preconditioning-induced cerebroprotection, as was pretreatment with the inducible NOS inhibitor aminoguanidine (400 mg/kg intraperitoneally). The protective effects of preconditioning were also not blocked by treating animals with competitive [3-(2-carboxypiperazin-4-yl)propyl-1-phosphonate; 5 mg/kg intraperitoneally] or noncompetitive (MK-801; 1 mg/kg intraperitoneally) N-methyl-D-aspartate receptor antagonists prior to preconditioning hypoxia. These findings indicate that NO production and activity are critical to the induction of ischemic tolerance in this model. However, the results argue against the involvement of the neuronal NOS isoform, activated secondary to a hypoxia-induced stimulation of N-methyl-D-aspartate receptors, and against the involvement of the inducible NOS isoform, but rather suggest that NO produced by the endothelial NOS isoform is required to mediate this profound protective effect.

Immunoreactivity for BER-EP4 in adenocarcinomas, adenomatoid tumors, and malignant mesotheliomas.

Ber-EP4 is a recently characterized monoclonal antibody directed against a cell surface glycoprotein that is putatively present on human epithelial cells but lacking on the mesothelium. To investigate the diagnostic efficacy of Ber-EP4 in distinguishing adenocarcinoma from mesothelioma, we studied formalin-fixed, paraffin-embedded sections from well-documented cases of adenocarcinoma (120 cases), adenomatoid tumor (nine cases), and malignant mesothelioma (49 cases). Of the 120 adenocarcinomas, 103 (86%) showed membranous Ber-EP4 positivity, with diffuse reactivity noted in 82 cases and focal staining in 21 cases. Reactivity with Ber-EP4 was also observed in two of nine adenomatoid tumors (22%) and 10 of 49 mesotheliomas (20%). Staining in the mesotheliomas was restricted to epithelioid areas and generally focal. In one mesothelioma, however, Ber-EP4 stained the majority of neoplastic cells. In contrast to previous reports, we conclude that positivity with Ber-EP4 does not exclude the diagnosis of mesothelioma. Nonetheless, most Ber-EP4-positive mesotheliomas exhibit only focal positivity, as opposed to the extensive staining commonly observed in adenocarcinomas. Ber-EP4 has diagnostic utility in the discrimination of mesothelioma from adenocarcinoma, but it is best utilized in an antibody panel that includes other markers of carcinomatous differentiation.

KATP channels mediate adenosine-induced hyperemia in retina.

PURPOSE: The authors and others have shown previously that the purine nucleoside adenosine is a potent vasodilator in the retinal microcirculation, mediating increases in retinal blood flow (RBF) in response to several autoregulatory stimuli. The current experiments were undertaken to elucidate the involvement of adenosine triphosphate (ATP)-sensitive potassium (KATP) channels and the adenylate cyclase--cyclic adenosine monophosphate (cAMP) second-messenger system in the transduction of adenosine's hyperemic response. METHODS: Retinal fluorescein angiograms were videorecorded in isoflurane-anesthetized newborn pigs, and changes in arteriovenous transit times and retinal arteriolar and venular diameters were used to estimate stimulus-induced changes in RBF. RESULTS: Intravitreal perivascular microsuffusion of 5 nmol and 50 nmol adenosine caused dose-dependent increases in RBF of 79% +/- 4% (P < 0.05; n = 5) and 323% +/- 61% (P < 0.05; n = 5), respectively. The KATP channel antagonist glibenclamide (0.5 nmol and 5 nmol) caused a significant, dose-dependent attenuation of the hyperemic response to 5 nmol adenosine. The specificity of glibenclamide for blocking KATP channels was demonstrated by its ability to block by 94% +/- 6% (P < 0.05; n = 5) the increase in RBF (94% +/- 7%; P < 0.05) elicited by the intravitreal microsuffusion of the KATP channel agonist cromakalim (5 nmol), whereas it had no effect on the 103% +/- 12% increase in RBF (P < 0.05; n = 5) induced by the nitric oxide donor sodium nitroprusside (15 nmol). Adenosine-induced hyperemia was not potentiated by forskolin (1.7 nmol; n = 4), an adenylate cyclase activator, and was not attenuated by dideoxyadenosine (5 nmol; n = 4), an adenylate cyclase inhibitor. In addition, no significant increases in RBF could be elicited by 2.5 to 25 nmol 8-bromo-cAMP (n = 4), a membrane-permeable cAMP analog. CONCLUSIONS: These results in the piglet indicate that adenosine increases blood flow in the retina by activating KATP channels, not by increasing in cyclic AMP secondary to adenylate cyclase activation. They also underscore the potential importance of KATP channels in the transduction of retinal vasodilatative responses to other agonists.

A clinicopathologic study of familial chronic lymphocytic leukemia.

The familial occurrence of chronic lymphocytic leukemia was studied using morphologic, immunophenotypic, cytogenetic, and immunoglobulin gene rearrangement analyses. Three of six siblings developed chronic lymphocytic leukemia. One (patient 1) died 9 years after the diagnosis of chronic lymphocytic leukemia at age 67 years. The other two patients, ages 64 and 68 years (patients 2 and 3, respectively), are alive after chronic lymphocytic leukemia was diagnosed 11 and 4 years ago, respectively. Using the Rye classification, patient 2 and patient 3 had Stage I and Stage O disease, respectively. In contrast, patient 1 had Stage IV disease. The bone marrow of patient 2 was 90% cellular, with sheets of mature lymphocytes, and that of patient 3 was 70% cellular, with a nodular pattern of similar cells. Both patients 2 and 3 had normal karyotypes. Immunophenotyping studies revealed that patient 3 had an expanded population of B cells with minimal to no detectable expression of surface immunoglobulins and membrane-bound light chains. In contrast, the B-cell population of patient 2 expressed immunoglobulins M, D, and Kappa light chains. Gene rearrangement studies performed on these two patients revealed different but distinct patterns of heavy chain rearrangement. This may represent an evolution of two different clones of chronic lymphocytic leukemia in this family.

Cerebral protection by hypoxic preconditioning in a murine model of focal ischemia-reperfusion.

Sublethal periods of hypoxia or ischemia can induce adaptive mechanisms to protect against subsequent lethal ischemic insults in a process known as ischemic preconditioning. In the present study, we developed a murine model of cerebral preconditioning using several common strains of adult mice. Animals were exposed to sublethal hypoxia (11% oxygen for 2 h) 48 h prior to a 90 min period of transient focal middle cerebral artery occlusion, induced by an intraluminal filament; injury was assessed 24 h later by TTC staining. Infarct volume in hypoxia-preconditioned animals was reduced 46%, 58%, and 64% in C57Bl/6, 129SvEv, and Swiss-Webster ND4 mice relative to their respective untreated controls. This non-invasive murine model of ischemic tolerance should be useful for elucidating the molecular basis of this protection using transgenic and knockout mice.

Effect of supplemental oxygen on supramaximal exercise performance and recovery in cystic fibrosis.

The effects of supplemental O2 on recovery from supramaximal exercise and subsequent performance remain unknown. If recovery from exercise could be enhanced in individuals with chronic lung disease, subsequent supramaximal exercise performance could also be improved. Recovery from supramaximal exercise and subsequent supramaximal exercise performance were assessed after 10 min of breathing 100% O2 or room air (RA) in 17 cystic fibrosis (CF) patients [25 +/- 10 (SD) yr old, 53% men, forced expired volume in 1 s = 62 +/- 21% predicted] and 17 normal subjects (25 +/- 8 yr old, 59% men, forced expired volume in 1 s = 112 +/- 15% predicted). Supramaximal performance was assessed as the work of sustained bicycling at a load of 130% of the maximum load achieved during a graded maximal exercise. Peak minute ventilation (VE) and heart rate (HR) were lower in CF patients at the end of each supramaximal bout than in controls. In CF patients, single-exponential time decay constants indicated faster recovery of HR (tau HR = 86 +/- 8 and 73 +/- 6 s in RA and O2, respectively, P < 0.01). Similarly, fast and slow time constants of two-exponential equations providing the best fit for ventilatory recovery were improved in CF patients during O2 breathing (tau 1VE = 132.1 +/- 10.5 vs. 82.5 +/- 10.4 s; tau 2VE = 880.3 +/- 300.1 vs. 368.6 +/- 107.1 s, P < 0.01). However, no such improvements occurred in controls. Supramaximal performance after O2 improved in CF patients (109 +/- 6% of the 1st bout after O2 vs. 94 +/- 6% in RA, P < 0.01). O2 supplementation had no effect on subsequent performance in controls (97 +/- 3% in O2 vs. 93 +/- 3% in RA). We conclude that supplemental O2 after a short bout of supramaximal exercise accelerates recovery and preserves subsequent supramaximal performance in patients with CF.

Neutrophil response to mucosal infection.

Total white cell counts were reviewed in paediatric in-patients with viral gastroenteritis, bacterial gastroenteritis, delayed recovery following acute gastroenteritis, viral lower respiratory tract infections and cow's milk protein intolerance. The prevalence of neutrophilia was not different in the five groups. Neutropenia was common in association with the presence of viruses in stool or sputum, and was significantly more common in these groups than in patients with bacterial gastroenteritis and cow's milk protein intolerance. Neutropenia has not been previously reported in viral gastroenteritis. It was transient in nature and not related to age, sex, weight or antibiotic treatment; no pancreatic disorders were noted.

Adenosine transport inhibition ameliorates postischemic hypoperfusion in pigs.

Cerebral ischemia is often followed by a period of delayed hypoperfusion that may contribute to tissue injury. We tested the hypothesis that augmentation of interstitial adenosine can improve tissue perfusion under this condition 10 min global ischemia was produced in two groups of isoflurane-anesthetized newborn pigs by occlusion of subclavian and brachiocephalic arteries, and changes in local cortical blood flow and cortical interstitial purine metabolites were measured using the combined hydrogen clearance-microdialysis technique. In one group, the dialysis probe was perfused with artificial cerebrospinal fluid buffer containing nitrobenzyl-thioinosine (NBT1, 100 mumol/l), a competitive inhibitor of adenosine transport. In the untreated group (n = 9), baseline cortical blood flow (39 +/- 3 ml/min/100 g) was depressed by 51 +/- 5% and 42 +/- 6% at 40 and 60 min, respectively, of postischemic reperfusion. NBTI increased baseline interstitial adenosine levels 2.4-fold which increased baseline cortical blood flow 1.5-fold to 60 +/- 4 ml/min/100 g, and increased both absolute adenosine levels as well as adenosine as a percentage of total purine metabolites throughout ischemia and reperfusion. As a result, the extent of postischemic hypoperfusion was significantly lessened in NBTI-treated animals (n = 9), with reductions in cortical blood flow of only 28 +/- 3% and 24 +/- 5% at 40 and 60 min of reperfusion, respectively. These results indicate that inhibition of adenosine transport by NBTI elevates interstitial adenosine concentration during and following cerebral ischemia, and concomitantly improves cortical perfusion in the post-ischemic period. The latter effect may contribute to the documented neuroprotective efficacy of adenosinergic therapy in cerebral ischemia.

Xanthine oxidase-derived superoxide causes reoxygenation injury of ischemic cerebral endothelial cells.

Oxygen free radicals, generated by cerebral ischemia, have been widely implicated in the damage of vascular endothelium. Endothelial cells have been proposed as a significant source of oxygen free radicals. In the present study, we developed an anoxia-reoxygenation (AX/RO) model using pure cultures of cerebral endothelial cells (CECs) isolated from piglet cortex to measure CEC oxygen free radical production and determine its role in AX/RO-induced CEC injury. CEC injury, as measured by lactate dehydrogenase efflux into the culture medium, increased progressively with the duration of anoxic exposure, becoming significant after 10 h. Reoxygenation significantly increased CEC anoxic injury in a time-dependent manner. A 55% increase in oxygen free radical production, determined by fluorescence detection of dihydroethidium oxidation, was measured at the end of 4-h reoxygenation in CECs subjected to AX/RO conditions that killed 40% of the cells. Blockade of oxygen free radical production with superoxide dismutase (SOD; 250 and 1000 U/ml) or oxypurinol (50 and 200 microM), a potent xanthine oxidase inhibitor, reduced this injury by 32-36% and 30-39%, respectively. Results from our in vitro model indicate that CECs produce significant amounts of oxygen free radicals following ischemia, primarily from the xanthine oxidase pathway. These radicals ultimately have a cytotoxic effect on the very cells that produced them. Thus, reductions in oxygen free radical-mediated vascular injury may contribute to improvements in neurophysiologic outcome following treatment with oxygen free radical inhibitors and scavengers.

Study of drug resistance in previously treated tuberculosis patients in Gujarat, India.

SETTING: Department of Tuberculosis and Chest Diseases and State Tuberculosis Diagnosis and Training Centre (STDTC), a DOTS centre in Ahmedabad, Gujarat State, India. The study was carried out by retrospectively reviewing patient data between January 2000 and August 2001. OBJECTIVE: To evaluate the pattern of drug resistance among previously treated tuberculosis patients who remained symptomatic or smear-positive despite receiving anti-tuberculosis drugs under DOTS for a minimum of 5 months. DESIGN: A total of 1472 pulmonary tuberculosis patients who had taken anti-tuberculosis treatment were evaluated retrospectively with respect to their drug resistance pattern by sputum culture for acid-fast bacilli (AFB) and sensitivity testing with isoniazid, rifampicin, streptomycin and ethambutol (E). RESULT: Of the 1472 patients evaluated, 804 (54.6%) were treatment failure cases and 668 (45.4%) were relapse cases; 822 patients (373 failure and 449 relapse) were culture-positive. Of these 822 patients, 482 (58.64%, 261 failure and 221 relapse) were resistant to one or more drugs. Resistance to one drug was observed in 86 patients (10.46%), to two drugs in 149 (18.13%), to three drugs in 122 (14.84%) and to four drugs in 125 (15.21%). Single drug resistance was most commonly seen with isoniazid (62 patients, 7.5%), followed by streptomycin (12 patients, 1.4%), rifampicin (eight patients, 0.97%) and ethambutol (four patients, 0.4%). Resistance to isoniazid plus rifampicin alone was seen in 76 patients (9.2%). CONCLUSION: Drug resistance is a major problem in the treatment of pulmonary tuberculosis. Detection of drug resistance patterns and treatment with second-line anti-tuberculosis drugs in appropriate regimens are necessary in the treatment of failure and relapse cases in order to reduce the emergence of multidrug-resistant tuberculosis.

Neuroprotection from ischemic brain injury by hypoxic preconditioning in the neonatal rat.

Very recent studies in adult gerbils and rats have shown that exposure to sublethal ischemia can confer neuroprotection from subsequent lethal ischemic episodes. To determine if a similar phenomenon can be elicited during the perinatal period, we have developed a preconditioning regimen that involves exposure to normothermic hypoxia (8% oxygen) 24 h prior to hypoxia-ischemia in the well-established post-natal-day 7 rat pup model [20]. Significant infarction, manifested as a 34 +/- 4% reduction in cerebral hemispheric weight ipsilateral to the carotid ligation, was noted in control animals (n = 24) one week after hypoxia-ischemia, whereas littermates preconditioned with 3 h hypoxia (n = 29) showed no evidence of hemispheric necrosis. Lack of injury in the latter animals was confirmed at the cellular level by histopathologic analyses of Nissl-stained coronal sections. Thus, pre-exposure to hypoxia induces endogenous adaptive mechanisms that can protect the perinatal brain from hypoxic-ischemic injury.

Considerations of anthropometric, tissue volume, and tissue mass scaling for improved patient specificity of skeletal S values.

It is generally acknowledged that reference man (70 kg in mass and 170 cm in height) does not adequately represent the stature and physical dimensions of many patients undergoing radionuclide therapy, and thus scaling of radionuclide S values is required for patient specificity. For electron and beta sources uniformly distributed within internal organs, the mean dose from self-irradiation is noted to scale inversely with organ mass, provided no escape of electron energy occurs at the organ boundaries. In the skeleton, this same scaling approach is further assumed to be correct for marrow dosimetry; nevertheless, difficulties in quantitative assessments of marrow mass in specific skeletal regions of the patient make this approach difficult to implement clinically. Instead, scaling of marrow dose is achieved using various anthropometric parameters that presumably scale in the same proportion. In this study, recently developed three-dimensional macrostructural transport models of the femoral head and humeral epiphysis in three individuals (51-year male, 82-year female, and 86-year female) are used to test the abilities of different anthropometric parameters (total body mass, body surface area, etc.) to properly scale radionuclide S values from reference man models. The radionuclides considered are 33P, 177Lu, 153Sm, 186Re, 89Sr, 166Ho, 32P, 188Re, and 90Y localized in either the active marrow or endosteal tissues of the bone trabeculae. S value scaling is additionally conducted in which the 51-year male subject is assigned as the reference individual; scaling parameters are then expanded to include tissue volumes and masses for both active marrow and skeletal spongiosa. The study concludes that, while no single anthropometric parameter emerges as a consistent scaler of reference man S values, lean body mass is indicated as an optimal scaler when the reference S values are based on 3D transport techniques. Furthermore, very exact patient-specific scaling of radionuclide S values can be achieved if measurements of spongiosa volume and marrow volume fraction (high-resolution CT with image segmentation) are known in both the patient and the reference individual at skeletal sites for which dose estimates are sought. However, the study indicates that measurements of the spongiosa volume alone may be sufficient for reasonable patient-specific scaling of S values for the majority of radionuclides of interest in internal-emitter therapy.

Effect of hypoglycemia on postischemic cortical blood flow, hypercapnic reactivity, and interstitial adenosine concentration.

Hypoglycemia increases the vulnerability of the perinatal brain to asphyxia, but it is not known if hypoglycemia-induced changes in cerebral hemodynamics and vascular reactivity underlie this vulnerability. This study tested the hypothesis that hypoglycemia exacerbates postischemic hypoperfusion, and impairs postischemic CO2 reactivity. The authors also examined the hypothesis that postischemic hypoperfusion is associated with a reduction in the interstitial concentration of the vasodilator metabolite adenosine. Global cerebral ischemia of 10 minutes duration was induced in newborn pigs anesthetized with isoflurane by occlusion of subclavian and brachiocephalic arteries; cortical cerebral blood flow (CBF) and interstitial adenosine concentration were evaluated simultaneously using the combined hydrogen clearance/microdialysis technique. Hypoglycemia (blood glucose < 25 mg/dl) was induced by regular insulin (25 IU/kg) administered intravenously 2 hours prior to induction of ischemia. In the eight normoglycemic animals, baseline CBF was 38 +/- 4 ml/min/100 gm and baseline adenosine concentration was 1.2 +/- 0.1 microM; in the eight hypoglycemic animals, these values were 39% (p < 0.05) and 62% (p < 0.05) greater, respectively, under baseline conditions. At 1 hour of postischemic reperfusion in normoglycemic animals, CBF was reduced 39% relative to the preischemic baseline (p < 0.01), concomitant with a 27% reduction (p < 0.05) in adenosine concentration, suggesting that this lowered concentration may underlie delayed hypoperfusion. These postischemic reductions in CBF and interstitial adenosine concentration were significantly greater in hypoglycemic animals, with CBF and adenosine concentration reduced 70% (p < 0.001) and 71% (p < 0.01), respectively, relative to baseline. In nine animals preischemic reactivity to hypercapnia was unaffected by hypoglycemia. Postischemic hypercapnic reactivity was retained in the eight normoglycemic animals, but was attenuated 73% (p < 0.05) in hypoglycemic animals. Thus, in the newborn pig, hypoglycemia exacerbates postischemic cortical hypoperfusion and impairs postischemic cerebrovascular reactivity to hypercapnia.