The role of cerebral blood flow and cerebrovascular reserve capacity in the diagnosis of chronic hydrocephalus--a PET-study on 60 patients.

AIM: To investigate the clinical value of cerebral blood flow (CBF) and cerebrovascular reserve capacity (CVR) in the management of chronic hydrocephalus. Global cortical CBF and CVR in 60 patients (66 +/- 12 yrs) with chronic hydrocephalus were investigated before, one week (7 d) and 7 months (7 m) after shunting by 15-O-H2O PET (Siemens ECAT 951/31) at rest and after application of acetazolamide (1 g). After 7 months, clinical outcome was assessed according to Stein and Langfitt and patients were classified into responder (n = 31) and non-responder (n = 29). Before Surgery, responder had lower blood flow values compared to non responder (36 +/- 8 vs. 41 +/- 11 ml/100 ml/min; p = 0.04), whereas CVR was not different between outcome groups (33 +/- 10 vs. 41 +/- 8%; p > 0.05). After shunting, CVR in non-responder decreased from 41 +/- 8% to 32 +/- 5% (7 d), whereas in responder significant increases (p < 0.02) to 55 +/- 46% (7 d) and 54 +/- 31% (7 m) were observed. Regarding early individual changes in CVR, the majority (12/18; 66%) of non-responder had marked decreases in CVR-levels (< 30%), whereas clinical responder considerably improved in CVR (> 30%) in half of patients (7/14). Measurement of cerebral blood flow in chronic hydrocephalus might substantially contribute to selection of shunt candidates and neurological sequels may be rather related to early regeneration of the hemodynamic reserve.

Regional cerebral blood flow profiles of shunt-responder in idiopathic chronic hydrocephalus--a 15-O-water PET-study.

AIM: To find out if regional characteristics of cerebral blood flow (CBF) and cerebrovascular reserve capacity (CVR) may indicate shunt response in idiopathic chronic hydrocephalus. 11 patients with idiopathic chronic hydrocephalus (65 +/- 13 yrs) were followed-up within a year after shunting. Patients were classified into clinical responder (n = 5) and non-responder (n = 6) according to Stein and Langfitt. All patients had measurement of CBF and CVR with dynamic 15-O-water PET (Siemens ECAT 951/31) before and after application of acetazolamide (1 g). Regional differences between outcome groups were analysed with "statistical Parametric Mapping" (SPM99b; Wellcome Department, London, UK). Group differences were regarded as significant, when uncorrected p-value on voxel and on cluster level were p < 0.001 and p < 0.05, respectively. Regarding CBF distribution there was significantly reduced CBF in the frontobasal cortex in responder compared to non-responder (cluster level p = 0.026). In CVR, a variety of cortical regions showed significant decreases compared with non-responder: also in frontobasal cortex (on cluster level p = 0.009). However, most significant reductions were found in temporodorsal and limbic cortical regions (on cluster level p < 0.001). Preoperative hemodynamics displayed a regional profile of reduced CBF and CVR in patients with shunt improvement. Prospective studies for determining the accuracy of regional blood flow characteristics for outcome prediction are warranted.

Monitoring isotretinoin therapy in thyroid cancer using 18F-FDG PET.

Treatment with isotretinoin (13-cis-retinoic acid, 13-cis-RA) is a recent additional option in advanced, otherwise intractable differentiated thyroid cancers. The aim of this study was to evaluate fluorine-18 fluorodeoxyglucose positron emission tomography (18F-FDG PET) in the prediction and the monitoring of response to 13-cis-RA therapy. Twenty-one patients with advanced differentiated thyroid cancers were investigated using 18F-FDG PET and iodine-131 whole-body scans before and 3, 6 and 9 months after initiation of 13-cis-RA therapy. After 9 months, 13-cis-RA treatment was discontinued and imaging procedures repeated 3 months later. Average 18F-FDG uptake (SUV) decreased significantly during 13-cis-RA therapy but subsequently increased in five of eight patients after withdrawal of 13-cis-RA. 18F-FDG uptake (SUV) 3 months after onset of 13-cis-RA therapy was significantly lower in patients who developed increased 131I uptake in their tumour sites than in patients with no subsequent increase in 131I uptake. There was no relationship between serum thyroglobulin level on the one hand and simultaneously measured 131I or 18F-FDG uptake on the other hand. There was a tendency towards lower 18F-FDG uptake in tumour manifestations with a better outcome. Therefore, 18F-FDG PET at 3 months after the start of treatment promises to differentiate between those patients who will eventually benefit from 13-cis-RA and those who will not. In conclusion, these data indicate that 18F-FDG PET is a useful tool for the evaluation and monitoring of adjuvant therapy with 13-cis-RA in thyroid cancer.

Biokinetics and imaging with the somatostatin receptor PET radioligand (68)Ga-DOTATOC: preliminary data.

Somatostatin (SMS) scintigraphy is widely used for the detection and staging of neuroendocrine tumours. Because of its superior imaging properties, there is growing interest in the use of positron emission tomography (PET) technology for SMS scintigraphy. This study addressed the production of gallium-68 DOTATOC, its biokinetics and its clinical performance in detecting SMS-positive tumours and metastases. A preparation protocol was developed, yielding 40% overall incorporation of (68)Ga into the peptide (DOTATOC). After column filtration, the radiochemical purity exceeded 98%. Eight patients with histologically verified carcinoid tumours were injected with 80-250 MBq of this tracer. PET acquisition was initiated immediately after administration and carried out until 3 h post injection. Images were quantitated using standardised uptake values and target to non-target ratios. Prior to (68)Ga-DOTATOC PET, all patients underwent indium-111 octreotide planar and single-photon emission tomographic (SPET) imaging. Arterial activity elimination was bi-exponential, with half-lives of 2.0 (+/-0.3) min and 48 (+/-7) min. No radioactive metabolites were detected within 4 h in serum. Maximal tumour activity accumulation was reached 70+/-20 min post injection. Kidney uptake averaged <50% compared with spleen uptake. Of 40 lesions predefined by computed tomography and/or magnetic resonance imaging, (68)Ga-DOTATOC PET identified 100%, whereas (111)In-octreotide planar and SPET imaging identified only 85%. Tumour to non-tumour ratios ranged from >3:1 for liver ((111)In-octreotide: 1.5:1) to 100:1 for CNS ((111)In-octreotide: 10:1). With (68)Ga-DOTATOC >30% additional lesions were detected. It is concluded that PET using (68)Ga-DOTATOC results in high tumour to non-tumour contrast and low kidney accumulation and yields higher detection rates as compared with (111)In-octreotide scintigraphy.

[1-(11)C]Acetate as a quantitative perfusion tracer in myocardial PET.

UNLABELLED: Our objective was to investigate the properties of [1-(11)C]acetate as a quantitative perfusion tracer for myocardial PET studies. METHODS: We determined the flow dependence of the effective acetate extraction by a comparison with [(13)N]ammonia in 24 patients at rest (n = 8) and under pharmacologic vasodilation (n = 16). Furthermore, we compared the statistical quality of the perfusion values derived with both tracers. Quantification was based on an irreversible 2-compartment model for [(13)N]ammonia and a reversible 1-compartment model for [1-(11)C]acetate. Area-conserving polar maps were used to determine the correlation between the unidirectional uptake parameters of both tracers on a pixel-by-pixel basis for the whole left ventricular myocardium. RESULTS: A fit of a generalized Renkin-Crone formula to the data yielded the unidirectional acetate extraction fraction E(f) = 1 - 0.64e(-1.20/f). An extraction correction based on this formula led to good quantitative agreement of perfusion values derived with [(13)N]ammonia and [1-(11)C]acetate over the whole observed flow range (average difference of flow values, 3%; correlation coefficient, 0.96). This agreement proved the applicability of acetate as a quantitative perfusion tracer even under stress conditions. An analysis of the statistical properties of the parameter estimates showed, moreover, that statistical errors were reduced by a factor of nearly 2 in comparison with ammonia. CONCLUSION: [1-(11)C]acetate allows accurate quantification of myocardial perfusion with PET at rest as well as under stress conditions. The use of acetate leads to distinctly improved statistical accuracy for the perfusion estimates in comparison with ammonia. This accuracy facilitates the generation of reliable parametric polar maps, which are especially useful for clinical application of myocardial perfusion quantification.

[Follow-up of differentiated thyroid cancer patients using rhTSH--preliminary results]. / Nachsorge des differenzierten Schilddrüsenkarzinoms unter Verwendung von rhTSH--vorläufige Ergebnisse.

AIM: In the follow-up of patients with advanced stage thyroid cancer radioiodine scintigraphy, F-18-FDG PET and tumormarker hTg using stimulation with recombinant human TSH (rhTSH) were compared to the results of same diagnostic procedures during TSH-suppression or endogenous TSH-stimulation. METHODS: 30 patients were investigated in hypothyroidism and after application of rhTSH regarding the serum hormone concentrations, hTg, radioiodine scans and FGD-PET scans. RESULTS: Radioiodine avidity and FDG uptake were significantly higher in 7/30 and 3/5 patients, respectively, compared to endogenous stimulation or TSH-suppression. In about one third of patients hTg increased more than 30%. CONCLUSION: Our preliminary results indicate a sufficient feasibility and sensitivity of rhTSH not only in the follow-up by hTg and radioiodine scan but also in FDG-PET.

Open finger tip healing and replacement after distal amputation in rhesus monkey with comparison to limb regeneration in lower vertebrates.

The left thumbs and great toes of three 8 1/2 month old Rhesus monkeys (Macaca mulatta) were amputated in guillotine fashion one millimeter distal to the base of the nail and allowed to heal by the conservative open wound method. Healing occurred in seven to ten days in these small digits. Each of the thumbs and toes grew back with some blunting and shortening of the digit tips, but were functional. The new structures were cosmetically pleasing as in the human instances. The nails grew essentially to normal size and shape supported by the remaining portions of the distal phalanges. Histological studies showed no evidence of blastema formation such as is observed in the regenerating limb of the Urodele (newt) taken as the comparative representative. The possibility of improving the regrowth is discussed against the background of our knowledge of the importance of nerve during limb regeneration in lower vertebrates.

Treatment of hand infections.

Microorganisms most commonly enter the tissues through wounds, large or small. Prevention involves keeping the hands clean by frequent washing and avoiding contamination. Early infections may be aborted by cleansing and antibiotics. If an established infection does not respond to a brief trial of heat, rest, elevation and antibiotics, incision and drainage should be carried out promptly, without waiting for fluctuation. Needle aspiration is not an adequate substitute for early surgical incision.

Functional exteriorized colon for perforations due to diverticulitis.

Three patients had normal bowel function with the sigmoid colon exteriorized through an abdominal wound for 39, 42 and 72 days. Colostomy was thus avoided during the time the patient was recovering from peritonitis and inflammation in the involved segment of colon. Ready access was provided to the distal limb of the colon at second operation.

Some results using triamcinolone on immobilized joints.

The frequency and causes of joint stiffness are reviewed. The most sophisticated repair may be for naught if the joints stiffen. Treatment of the established condition leaves much to be desired. Since mobility cannot be maintained during many postoperative periods and during the treatment of many conditions, any aid to prophylaxis is desirable especially if the side effects are negligible. Steroids have been chosen because of their influence on collagen metabolism and because much is known of their toxicity and side effects. The drug was first given into the knee joints of rats where it was found effective in preventing joint stiffness in joints immobilized three weeks. In view of the animal success, fourteen patients with thenar pedicles have had a single dose of triamcinolone injected into the peri-articular tissues of their proximal interphalangeal joints at the time of construction of the pedicle. Follow up observation shows all patients to have complete proximal interphalangeal joint extension and flexion to 95 degrees. Side effects were minimal.

Occult adrenal insufficiency in surgical patients.

Eight patients admitted to a University hospital with acute surgical problems and related adrenal insufficiency were reviewed and three are presented in detail. Surgical stress and continued sepsis played major roles in the lack of responsiveness to usual modes of therapy until the adrenal insufficiency was corrected. The patients fell into three major clinical categories of adrenal insufficiency. Chronic illness and sepsis are shown to affect steroid production and metabolism, as well as adrenal responsiveness to ACTH. Pharmacologic amounts of steroids are often needed in patients with shock, gram negative sepsis and prolonged illnesses, even if normal or elevated serum cortisols are present. Therapeutic trials of cortisol administration are shown to be confusing when not accompanied by easily performed diagnostic tests of adrenal function. It is emphasized that a pretreatment serum cortisol should be obtained whenever possible. The evaluation of adrenal function is of lifelong importance to the patient.