Outcomes and predictors of response from an optimised, multidisciplinary intervention for chronic fatigue states.

BACKGROUND: Medically unexplained chronic fatigue states are prevalent and challenging to manage. Cognitive behavioural therapy (CBT) and graded exercise therapy (GET) are effective in clinical trials. The evaluation of delivery in a standard healthcare setting is rare. An integrated treatment programme with individualised allocation of resources to patients' needs was developed and implemented through an academic outpatient clinic. It was hypothesised that the programme would result in similar responses to those observed in the clinical trials. AIM: To evaluate the outcomes of an integrated, 12-week CBT and GET programme delivered by exercise physiologists and clinical psychologists. METHODS: Consecutive eligible patients (n = 264) who met the diagnostic criteria for chronic fatigue syndrome or post-cancer fatigue were evaluated with self-report measures of fatigue, functional capacity and mood disturbance at baseline, end-of-treatment (12 weeks) and follow-up (24 weeks). A semi-structured interview recording the same parameters was conducted pre- and post-treatment by an independent clinician. Primary outcome was analysed by repeated measures analysis of variance and predictors of response were analysed by logistic regression. RESULTS: The intervention produced sustained improvements in symptom severity and functional capacity. A substantial minority of patients (35%) gained significant improvement, with male gender and higher pain scores at baseline predicting non-response. A small minority of patients (3%) worsened. CONCLUSION: The manualised protocol of integrated CBT and GET was successfully implemented, confirming the generally positive findings of clinical trials. Assessment and treatment protocols are available for dissemination to allow standardised management. The beneficial effects described here provide the basis for ongoing studies to optimise the intervention further and better identify those most likely to respond.

We should count ourselves lucky.

Last summer I was extremely lucky to have the opportunity to visit Harvard School of Dental Medicine for my elective. I now return to my final year of dental school in Manchester with a renewed sense of appreciation for the education system I have entered in to. I was shocked at the price dental students in America pay to receive an education, and at some of their unusual practices along the way.

The nss mutation or lanthanum inhibits light-induced Ca2+ influx into fly photoreceptors.

Ion-selective calcium microelectrodes were inserted into the compound eyes of the wild-type sheep blowfly Lucilia or into the retina of the no steady state (nss) mutant of Lucilia. These electrodes monitored light-induced changes in the extracellular concentration of calcium (delta[Ca2+]o) together with the extracellularly recorded receptor potential. Prolonged dim lights induced a steady reduction in [Ca2+]o during light in the retina of normal Lucilia, while relatively little change in [Ca2+]o was observed in the retina of the nss mutant. Prolonged intense light induced a multiphasic change in [Ca2+]o: the [Ca2+]o signal became transient, reaching a minimum within 6 s after light onset, and then rose to a nearly steady-state phase below the dark concentration. When lights were turned off, a rapid increase in [Ca2+]o was observed, reaching a peak above the dark level and then declining again to the dark level within 1 min. In analogy to similar studies conduced in the honeybee drone, we suggest that the reduction in [Ca2+]o reflects light-induced Ca2+ influx into the photoreceptors, while the subsequent increase in [Ca2+]o reflects the activation of the Na-Ca exchange which extrudes Ca2+ from the cells. In the nss mutant in response to intense prolonged light, the receptor potential declines to baseline during light while the Ca2+ signal is almost abolished, revealing only a short transient reduction in [Ca2+]o. Application of lanthanum (La3+), but not nickel (Ni2+), into the retinal extracellular space of normal Lucilia mimicked the effect of the nss mutation on the receptor potential, while complete elimination of the Ca2+ signal in a reversible manner was observed. The results suggest that La3+ and the nss mutation inhibit light-induced Ca2+ influex into the photoreceptor in a manner similar to the action of the trp mutation in Drosophila, which has been shown to block specifically a light-activated Ca2+ channel necessary to maintain light excitation.

Genetic dissection of light-induced Ca2+ influx into Drosophila photoreceptors.

Invertebrate photoreceptors use the inositol-lipid signaling cascade for phototransduction. A useful approach to dissect this pathway and its regulation has been provided by the isolation of Drosophila visual mutants. We measured extracellular changes of Ca2+ [delta Ca2+]o in Drosophila retina using Ca(2+)-selective microelectrodes in both the transient receptor potential (trp) mutant, in which the calcium permeability of the light-sensitive channels is greatly diminished and in the inactivation-but-no-afterpotential C (inaC) mutant which lacks photoreceptor-specific protein kinase C (PKC). Illumination induced a decrease in extracellular [Ca2+] with kinetics and magnitude that changed with light intensity. Compared to wild-type, the light-induced decrease in [Ca2+]o (the Ca2+ signal) was diminished in trp but significantly enhanced in inaC. The enhanced Ca2+ signal was diminished in the double mutant inaC;trp indicating that the effect of the trp mutation overrides the enhancement observed in the absence of eye-PKC. We suggest that the decrease in [Ca2+]o reflects light-induced Ca2+ influx into the photoreceptors and that the trp mutation blocks a large fraction of this Ca2+ influx, while the absence of eye specific PKC leads to enhancement of light-induced Ca2+ influx. This suggestion was supported by Ca2+ measurements in isolated ommatidia loaded with the fluorescent Ca2+ indicator, Ca Green-5N, which indicated an approximately threefold larger light-induced increase in cellular Ca2+ in inaC relative to WT. Our observations are consistent with the hypothesis that TRP is a light activated Ca2+ channel and that the increased Ca2+ influx observed in the absence of PKC is mediated mainly via the TRP channel.

Inhibition of in vitro hematopoiesis by hepatitis A virus.

Inoculation of human bone marrow with hepatitis A virus (HAV) resulted in a dose- and duration-of-incubation-dependent suppression of hematopoietic progenitor (CFU-GM, BFU-E, CFU-Mix) growth in vitro. Monocytic progenitors appeared to be least affected. While HAV inactivation by heat or beta-propiolactone and neutralization by specific antibodies completely abrogated hematopoietic inhibition, depletion of adherent bone marrow cells, and enrichment of progenitors did not alter the pattern of suppression, which also seemed to be independent of HuIFN-alpha, -beta, -gamma, and TNF. These findings support the concept that direct infection of progenitor cells by HAV may be responsible for hematologic changes commonly seen during early phases of infectious hepatitis and possibly for some cases of bone marrow failure.

100 living-related kidney donor evaluations using digital subtraction angiography.

Intravenous digital subtraction angiography (IV-DSA) combined with excretory urography was used to evaluate the renal anatomy of 100 potential living-related kidney donors. Each of the 100 patients underwent subsequent nephrectomy to verify the number and distribution of renal vessels. For the entire series, 71 patients had bilateral single, 2 bilateral multiple and 27 multiple renal arteries on one side determined by angiography. Eleven patients required standard catheter angiography due to inadequate IV-DSA studies. Four patients who had a single artery imaged by IV-DSA were found to have an additional vessel at the operation. The overall accuracy of IV-DSA to identify the number of renal vessels was 96% (85/89). The sensitivity of the exam was 100% (94/94) and the specificity was 67% (4/6). It is concluded that IV-DSA combined with excretory urography is a safe, cost effective, and suitable method to image the renal anatomy of potential kidney donors. Thus about 90% of donors can be spared the risks and inconvenience of standard angiography, and the donor evaluation can now be performed on an outpatient basis.

Comparative evaluation of urographic contrast media, inulin, and 99mTc-DTPA clearance methods for determination of glomerular filtration rate in clinical transplantation.

Plasma clearance of inulin (Cin), 99mTc-DTPA (CDTPA), and urographic contrast media (CCM) were determined simultaneously in 31 patients with varying levels of renal function evaluated in the setting of affiliated cardiac and renal transplantation programs. Cin and CDTPA were calculated from the ratio of simultaneously measured plasma concentration and urine excretion rate of these test agents (UxV/P). CCM was derived from x-ray fluorescence measurement of plasma iodine (PI) content following intravenous injection of 50 ml of nonionic, low-osmolar contrast media (180 mg I/ml). Urine collections were not required for CCM determinations. No adverse reactions attributable to CM occurred in any patient, and follow-up serum-creatinine values did not differ significantly from prestudy levels. CCM determined from the rate of decline in PI between 3 hr and 4 hr following administration of contrast media ("slope-intercept" technique) [Ccm-SI] correlated closely with corresponding levels of Cin (r = .86, P less than 0.0001). and CDTPA (r = 0.89, P less than 0.0001). Mean CCM-SI/Cin and CCM-SI/CDTPA ratios for the entire study cohort were 1.09 +/- 0.06 and 1.08 +/- 0.06, respectively. CCM-SI determinations also correlated well with CCM levels derived from a single measurement of PI ("single sample" technique) made at 3 hr following injection of contrast media (r = 0.94, P less than 0.0001). Both CCM-SI and CCM determined by the "single sample" method (CCM-3 degrees SS) tended to overestimate Cin and CDTPA, however, when the latter were less than 20 ml/min/1.73 m2 (mean CCM-SI/Cin and Ccm-3 degrees SS/Cin ratios 1.36 +/- 0.14 and 1.95 +/- 1.0, respectively. Reproducibility was evaluated by paired comparison of 3-hr vs. 4-hr "single sample" CCM determinations (r = 0.99, P less than 0.0001). In addition, analysis of the variation in iodine content between duplicate specimens obtained at each of these time intervals revealed a mean ratio of 1.0 +/- 0.01 (P = NS vs. identity). Contrast clearance determination utilizing the slope-intercept method is accurate, safe, pragmatic, and more precise than serum-creatinine and endogenous-creatinine clearance for measurement of renal function in clinical transplantation.

Scintigraphic demonstration of lower extremity periostitis secondary to venous insufficiency.

The scintigraphic findings on bone imaging in two patients with extensive lower extremity periostitis secondary to venous insufficiency are presented. One of these patients had bilateral disease. The use of [67Ga]citrate scanning in an attempt to exclude concurrent osteomyelitis is also addressed.

Controlled endoscopic retrieval of ectopic ureteral catheters using fluoroscopic guidance.

The double-J ureteral catheter has been popularized as an ideal internal ureteral stent. Migration of the distal end of the catheter up the ureter, however, can complicate its safe removal. A safe, controlled method of stent extraction is described using a C-arm fluoroscopic unit.

Correlation of radionuclide and ultrasound studies with biopsy findings for diagnosis of renal transplant rejection.

The diagnosis of early renal transplant rejection is of the utmost importance to the transplant recipient. Unfortunately, such a diagnosis is often extremely difficult to make. In an attempt to clarify this issue we retrospectively evaluated 35 patients with the presenting diagnosis of rejection for the correlation of comparable radionuclide (RN) and ultrasound (US) examinations with biopsy findings. In 21 patients with heavy interstitial mononuclear cell infiltration, 22 of 23 serial RN studies within forty-eight hours of biopsy were positive for rejection. Only 3 of 14 comparable US studies were positive for rejection. When examinations performed within approximately fourteen days were evaluated, 7 of 11 RN studies were positive for rejection, while 2 of 9 comparable US studies were positive for rejection. However, in 14 patients with mild or no interstitial cellular infiltration, only 6 of 13 RN studies were positive, while all 4 US examinations were negative. In the group evaluated at approximately two weeks, 2 of 6 RN studies were positive, while 0 of 5 US studies were positive. We conclude that the serial RN study is more sensitive than US examination for the diagnosis of acute rejection. US, however, proved valuable in the identification of transplant complications (i.e., fluid collections, ascites, and hydronephrosis).

Management of extraperitoneal bladder rupture.

Extraperitoneal bladder ruptures secondary to blunt trauma are caused by fractures of the bony pelvis 95 per cent of the time. A static cystogram is the only way to diagnose the lesion definitely. We have treated our 41 patients successfully with catheter drainage alone despite extensive urinary extravasation. Eighty-seven per cent of the ruptures will be healed in 10 days, and virtually all will be healed in 3 weeks.

Urethrography in the diagnosis of acute urethral injuries.

Urethrography has proved to be tremendously valuable in the evaluation of patients with suspected acute urethral injuries. The authors review the techniques of examination, the anatomy, and the urethrographic classification of acute injuries in the male patient.

Provocative imaging. Diuretic renography.

Diuretic renography remains the noninvasive functional study of choice in patients with hydronephrosis resulting from apparent UPJ obstruction. Meticulous attention to proper patient preparation, radiopharmaceutical selection, furosemide dosage and administration, and image interpretation and an awareness of potential pitfalls are essential for accurate diagnosis. For most patients, the F + 20 protocol is sufficient, however; the F-15 protocol allows clarification in cases of equivocal baseline F + 20 studies. Invasive antegrade techniques such as the Whitaker pressure/perfusion test are best reserved for patients in whom the diagnosis remains equivocal after diuretic renography, or in patients with massive hydronephrosis or renal insufficiency. New standardized protocol guidelines should help to ensure studies that are reproducible in different nuclear medicine laboratories.

Computed tomography of the kidney.

The development and refinement of computed tomography have revolutionized the diagnostic evaluation of patients in urologic practice. This article reviews the applications and interpretation, as well as the limitations, of renal computed tomography and compares this modality with other imaging studies of the kidney.

The indeterminate renal mass.

Ultrasound and CT scan play complimentary roles for the evaluation of indeterminate renal masses. Fast MR imaging with and without gadolinium is performed for characterization of renal masses when patients have a contraindication to iodinated contrast material. Radiologists have a primary role in detecting and managing indeterminate renal masses.

Radiology of the bladder and urethra in blunt pelvic trauma.

Appropriate radiologic studies are mandatory for assessing the extent and nature of lower urinary tract injuries following blunt pelvic trauma. A flow sheet summarizing these radiographic studies is presented in Figure 24. With pelvic fracture, two injuries may be found--extraperitoneal rupture of the bladder and rupture of the posterior urethra. In some patients, these injuries may be combined. Intraperitoneal rupture of the bladder occurs as a result of a blow to the lower abdomen or pelvis in patients whose urinary bladder is distended at the time of injury. A pelvic fracture may or may not be present. Anterior urethral injuries are more commonly associated with instrumentation in the male patient; they may, however, occur as a result of blunt injury to the external genitalia or perineum.

Computed tomography in blunt trauma.

Until now, CT has been utilized very little in the evaluation of the bluntly traumatized patient. Based on our early experience, we have attempted to demonstrate the CT features of a spectrum of injuries. Much of this information is new and additional studies will have to be performed to elucidate fully the benefits of computed tomography in the diagnosis of trauma. A method of study has been outlined which stresses the use of intravascular, oral, and, when needed, rectal contrast materials for study in these patients.

Guided cyst puncture and aspiration.

With the widespread acceptance of ultrasonography and computed tomography for the evaluation of renal masses, the role of guided renal cyst puncture in the evaluation of a suspected renal cyst has undergone revision in recent years. In this article, the authors review the technique, interpretation, and complications of diagnostic cyst puncture and attempt to define its current diagnostic and therapeutic indications.

Percutaneous cholecystostomy and lithotripsy of gallstones.

Extracorporeal lithotripsy has a high incidence of postprocedure biliary colic and slow disappearance of gallstones. This situation has led to the development of a new technique which has been successful in four patients and consists of percutaneous cholecystostomy, direct stone visualization, and fragmentation of gallstones with a percutaneous lithotripter. All patients had a functioning gallbladder, stone diameter less than 30 mm, and abdominal pain secondary to cholelithiasis. The procedure was performed in a two day hospitalization. Initially, under general anesthesia, the gallbladder was intubated with a 21 gauge needle and guidewire and the tract dilated to #30 French. A nephroscope was advanced into the gallbladder through a rigid sheath. All gallstones were visualized, fragmented with a percutaneous lithotripter, and extracted. After a postoperative cholecystocholangiogram, an self-retaining catheter was placed in the gallbladder for an average of 2.5 days. Three of the four patients were discharged from the hospital in two days without any complications. A fourth patient had a small bile leak treated with antibiotics. After an average of 13 months follow-up, all patients had a normal ultrasound or oral cholecystogram and no biliary tract symptoms. This technique is safe and efficient in removing gallstones and has no recurrence of gallstones in the 13 month follow-up period.