South African guidelines for receptor radioligand therapy (RLT) with Lu-177-PSMA in prostate cancer.

BACKGROUND: Prostate cancer is an important cause of morbidity and mortality in South Africa, as it is in the rest of the world. In African men, however, prostate cancer tends to follow a more aggressive course when compared to their European counterparts. This is attributed to a plethora of diverse factors of which an underlying genetic component has been shown to be an important aspect. Such differences highlight the need for individualised therapy and for local guidelines. The aim of this guideline is to aid nuclear physicians and other clinicians who manage patients with prostate cancer in the correct identification and treatment of patients who are likely to benefit from receptor radioligand therapy. RECOMMENDATIONS: There are a multitude of treatment modalities available for the treatment of prostate cancer and these therapies may be required at various time points during the course of the disease in any individual patient. A multidisciplinary approach is crucial in deciding which therapy, or combination of therapies, would be most advantageous at particular time points. The multidisciplinary team should include a urologist, oncologist and nuclear medicine physician as a minimum, and should ideally also involve a palliative/pain specialist, a dietician and a psychologist. CONCLUSION: Treatment with 177Lu-PSMA has emerged as a promising systemic modality, which involves the delivery of targeted radiation therapy in the form of ß-particles to sites of tumour tissue. Therapy is provided on an outpatient basis, is well tolerated with relatively few side effects and has a positive effect on overall survival and quality of life. At present, it is used mostly in the setting of advanced, castrate-resistant cancer. Patients are selected (amongst other criteria) based on the prior PSMA-based SPECT/PET/CT imaging (99mTc-,68Ga- or 18F-PSMA), which should demonstrate sufficient receptor expression in order to consider PSMA-based targeted radionuclide therapy. Such imaging of an intended target prior to its therapeutic targeting is known as a theranostic approach.

Coupled optical resonance laser locking.

We have demonstrated simultaneous laser frequency stabilization of a UV and IR laser, to coupled transitions of ions in the same spectroscopic sample, by detecting only the absorption of the UV laser. Separate signals for locking the different lasers are obtained by modulating each laser at a different frequency and using lock-in detection of a single photodiode signal. Experimentally, we simultaneously lock a 369 nm and a 935 nm laser to the (2)S(1/2) → (2)(P(1/2) and (2)D(3/2) → (3)D([3/2]1/2) transitions, respectively, of Yb(+) ions generated in a hollow cathode discharge lamp. Stabilized lasers at these frequencies are required for cooling and trapping Yb(+) ions, used in quantum information and in high precision metrology experiments. This technique should be readily applicable to other ion and neutral atom systems requiring multiple stabilized lasers.

Diagnosis and management of Pompe disease.

Pompe disease (PD) is an autosomal-recessively inherited neuromuscular disease that, if not diagnosed and treated early, can be fatal. It can present from early infancy into adulthood. Due to the lack of acid alpha-glucosidase, there is progressive intracellular accumulation of glycogen. The severity of the disease is determined by age of onset, organ involvement including the degree of severity of muscle involvement, as well as rate of progression. PD is classified into two groups: infantile and late-onset, each having two subgroups. The need for two tests performed by separate methods (screening and confirmatory) is outlined. It is imperative to try to reduce the time to diagnosis and to recognise the possibilities of false-positive results. A multidisciplinary team approach to treatment of affected patients is optimum with, as team leader, a physician who has experience in managing this rare disorder. In this article, we present a brief overview of the disease and provide guidelines for diagnosis and management of this condition in South Africa.

Crystalloid preload versus rapid crystalloid administration after induction of spinal anaesthesia (coload) for elective caesarean section.

Current methods of crystalloid preload administration prior to spinal anaesthesia for elective caesarean section are relatively ineffective in preventing hypotension. This study examined the relevance of the timing of the fluid administered. Fifty women were randomly allocated to receive either 20 ml x kg(-1) of crystalloid solution during 20 minutes prior to induction of spinal anaesthesia (preload), or an equivalent volume by rapid infusion immediately after induction (coload). Significantly more patients in the coload group did not require vasopressor therapy pre-delivery (P=0.047). The coload group required a lower median dose (P=0.03) and a lower median number (P=0.04) of ephedrine doses for the treatment of maternal hypotension pre-delivery. There was no between-group difference in either the total cumulative dose, or in the total number of doses of ephedrine. Neonatal outcomes among the two groups were similar. Rapid crystalloid administration after, rather than over 20 minutes before the induction of spinal anaesthesia for elective caesarean section, may be advantageous in terms of managing maternal blood pressure prior to delivery.

Cognitive aspects of chronic depression.

Previous research on chronic depression has focused on its link with other mood disorders and Axis II personality disorders. However, there are few data examining whether the cognitive perspective applies to this condition. In this cross-sectional study, 42 outpatients with chronic depression were compared with 27 outpatients with nonchronic major depressive disorder and 24 never psychiatrically ill controls on cognitive variables thought to be related to vulnerability to depression (e.g., dysfunctional attitudes, attributional style, a ruminative response style, and maladaptive core beliefs). Both depressed groups were more elevated than a never-ill comparison group. However, chronically depressed individuals were generally more elevated on measures of cognitive variables than those with major depressive disorders even after controlling for mood state and personality disorder symptoms.

Long-term employment outcomes in a rural area following traumatic brain injury.

One of the major sequelae following traumatic brain injury is a change in employment status. This poses significant challenges for rehabilitation services. Several studies have investigated the longer-term outcome after traumatic brain injury. Longer-term outcome in an economically disadvantaged rural environment with limited rehabilitation services has not been studied extensively. A group of individuals (n = 65) who sustained a traumatic brain injury were compared regarding pre- and post-employment status. The moderate and severely injured sub-groups showed a significant change in employment status. Ideally rehabilitation programs should target re-employment as an outcome. Limited employment opportunities in rural areas may make this more difficult to achieve.

Identification of a tyrosine kinase-phosphorylated protein in arachidonic acid- and prostaglandin A(2)-treated cells in vitro.

The effects of 20 microg/ml exogenous arachidonic acid (AA) and prostaglandin A(2) (PGA(2)) were evaluated on total tyrosine kinase (TK) activity and tyrosine phosphorylation status in HeLa and MCF-7 cells. AA and PGA(2) increased TK activity in both HeLa and MCF-7 cells. Western blotting employing an anti-phosphotyrosine antibody showed only one protein of approximately 55 kDa (approximately 55 kDa) to be phosphorylated in the MCF-7 cells, while a variety of proteins were phosphorylated in the HeLa cells, including the approximately 55 kDa protein. Amino acid analyses as well as Matrix Assisted Laser Desorption Ionization were conducted on this protein from different cell lines and it was shown to be similar. Comparison to p53 did not show similarities. The identity of this protein needs to be further characterized to help elucidate the signal transduction pathways of AA and PGA(2).

Comparison of obsessive-compulsive disorder patients with and without comorbid putative obsessive-compulsive spectrum disorders using a structured clinical interview.

Increasing attention has been paid to the possibility that a range of disorders, the putative obsessive-compulsive spectrum disorders (OCSDs), may share overlapping phenomenological and neurobiological features with obsessive-compulsive disorder (OCD). The development of a structured clinician-administered interview for the putative OCSDs (SCID-OCSD) is described. This instrument was used to investigate differences between OCD patients with a comorbid putative OCSD and OCD patients without a comorbid putative OCSD. A sample of 85 adult patients (38 men and 47 women) presenting for treatment of OCD was interviewed with the SCID-OCSD. OCD patients without comorbid putative OCSDs (n = 36) were compared to patients with comorbid OCSDs (n = 49) in terms of demographic features, clinical characteristics, and associated comorbidity with other non-OCSD DSM-IV axis I disorders. Of the OCD patients, 57.6% currently met criteria for at least one putative OCSD and 67.1% had a lifetime history of at least one comorbid OCSD. The OCSDs with the highest prevalence rates were compulsive self-injury (22.4%), compulsive buying (10.6%), and intermittent explosive disorder (10.6%). There was a significantly larger proportion of women in the group with comorbid OCSDs. Although the two groups did not differ in terms of severity of OCD symptoms, the group with comorbid OCSDs had significantly more obsessions and compulsions. The two groups did not differ significantly in terms of associated psychopathology other than OCSDs. We conclude that the SCID-OCSD provides clinicians and researchers with an instrument for the diagnosis of putative OCSDs. Our findings suggest that putative OCSDs have a relatively high prevalence rate in OCD patients. In addition, OCD patients with comorbid OCSDs differ with regard to certain demographic and clinical features. Further research, particularly genetic and neuroimmunological work, may ultimately be useful in validating the obsessive-compulsive spectrum.

Association between a catechol-o-methyltransferase polymorphism and obsessive-compulsive disorder in the Afrikaner population.

BACKGROUND: It has been proposed that the catechol-o-methyl transferase gene (COMT) may play a role in the pathogenesis of obsessive-compulsive disorder (OCD). Whereas studies in a North American population showed that the low activity (L) allele of a functional polymorphism in COMT was associated with OCD in male patients, this result was not supported by studies in a Japanese population. The present association study assessed the risk for OCD conferred by this COMT polymorphism in a geographically different patient group, namely, the relatively genetically homogeneous Afrikaner population of South Africa. METHODS: Fifty-four unrelated OCD patients and fifty-four sex-matched controls were recruited from the same Afrikaner community. Patients and controls were phenotyped (DSM-IV) and genotyped for a NlaIII polymorphism with H (high activity) or L (low activity) alleles in the COMT gene. RESULTS: The H/L genotype was significantly more common than expected in the OCD patient group (P = 0.0017). LIMITATIONS: Replication studies with related individuals may be useful in discovering factors underpinning the H/L genotype abundance in the Afrikaner population. CONCLUSIONS: These results emphasise the need for further studies in genetically homogeneous populations to help define the complex etiology of this disease.

Characteristics and phenomenology of hair-pulling: an exploration of subtypes.

This study was designed to detail the demographic and phenomenological features of adult chronic hair-pullers. Key possible subtypes were identified a priori. On the basis of the phenomenological data, differences between the following possible subtypes were investigated: hair-pullers with and without DSM-IV trichotillomania (TTM), oral habits, automatic versus focused hair-pulling, positive versus negative affective cues prior to hair-pulling, comorbid self-injurious habits, obsessive-compulsive disorder (OCD), and tics. Forty-seven participants were drawn from an outpatient population of chronic adult hair-pullers. A structured interview that focused on hair-pulling and associated behaviors was administered to participants. Six of the participants (12.8%) were male, and 41 (87.7%) were female. A large number of hair-pullers (63.8%) had comorbid self-injurious habits. A greater proportion of male hair-pullers had comorbid tics when compared with females. Certain subgroups of chronic hair-pullers (e.g., hairpullers with or without automatic/focused hair-pulling, comorbid self-injurious habits, and oral habits) were found to differ on a number of phenomenological and hair-pulling characteristics. However, differences between other possible subgroups (e.g., hair-pullers with or without DSM-IV TTM, comorbid OCD, and negative versus positive affective cues) may reflect greater severity in hair-pulling symptomatology rather than distinct subtypes of chronic hair-pulling. The findings of the present study also indicated that chronic hair-pulling (even in cases where DSM-IV criteria for TTM were not met) has a significant impact on quality of life. The present study provided limited support for the existence of possible subtypes of chronic hair-pulling. Recommendations are made for further investigations into such subtypes.

Implementation of a Tc-99m and Ce-139 scanning line source for attenuation correction in SPECT using a dual opposing detector scintillation camera.

Image degradation during single photon emission computed tomography (SPECT) due to attenuation and Compton scatter of photons can cause clinical image artifacts and will also result in inaccurate quantitative data. Therefore attenuation correction methods recently received wide interest. Transmission imaging can be performed to obtain the attenuation coefficients of a nonhomogeneous attenuating medium accurately. The aim of this study was firstly to evaluate the imaging characteristics of the scanning line source assembly. The results obtained with Tc-99m and Ce-139 were compared. Secondly the calculated attenuation coefficients were compared with known values from literature, using Tc-99m and Ce-139 as transmission sources. Lastly the method of acquiring simultaneous transmission and emission data was investigated. This study shows that an attenuation coefficient map can be obtained using a scanning line source for transmission imaging with a dual opposing detector camera. The imaging characteristics of Tc-99m and Ce-139 as transmission sources are similar. The resolution obtained with the Ce-139 line source was poorer than that obtained with the Tc-99m line source. A linear relationship was found between CT numbers and attenuation coefficients for transmission images using both Tc-99m and Ce-139 line sources. The attenuation coefficient value for water was underestimated by 1% using the Tc-99m transmission source and underestimated by 10% using Ce-139 as transmission source. This underestimation of attenuation coefficient values was also obtained in the human study. A myocardial perfusion study processed without and with attenuation correction clearly demonstrated the effect of the attenuation correction in the inferior myocardial region. The potential of using a scanning line source as transmission source with a dual opposing detector camera has been demonstrated in this study. The transmission source, Ce-139 was successfully introduced in this investigation for simultaneous acquisition of transmission and emission data.

Incidence and causes of tenosynovitis of the wrist extensors in long distance paddle canoeists.

OBJECTIVES: To investigate the incidence and causes of acute tenosynovitis of the forearm of long distance canoeists. METHOD: A systematic sample of canoeists competing in four canoe marathons were interviewed. The interview included questions about the presence and severity of pain in the forearm and average training distances. Features of the paddles and canoes were determined. RESULTS: An average of 23% of the competitors in each race developed this condition. The incidence was significantly higher in the dominant than the nondominant hand but was unrelated to the type of canoe and the angle of the paddle blades. Canoeists who covered more than 100 km a week for eight weeks preceding the race had a significantly lower incidence of tenosynovitis than those who trained less. Environmental conditions during racing, including fast flowing water, high winds, and choppy waters, and the paddling techniques, especially hyperextension of the wrist during the pushing phase of the stroke, were both related to the incidence of tenosynovitis. CONCLUSION: Tenosynovitis is a common injury in long distance canoeists. The study suggests that development of tenosynovitis is not related to the equipment used, but is probably caused by difficult paddling conditions, in particular uneven surface conditions, which may cause an altered paddling style. However, a number of factors can affect canoeing style. Level of fitness and the ability to balance even a less stable canoe, thereby maintaining optimum paddling style without repeated eccentric loading of the forearm tendons to limit hyperextension of the wrist, would seem to be important.

Cytotoxicity of combined essential fatty acids on a human prostate cancer cell line.

In this study the effect of single and concomitantly added n-6 or n-3 polyunsaturated fatty acids (PUFAs) was investigated on human prostate cells. Data obtained from the single fatty acids (FAs) experiments showed that except for oleic acid (OA), arachidonic (AA) and linoleic acid (LA), which had very little (less than 10% cells dead) effect on the cells, an increase in dead cells was observed at physiological concentrations of, eicosapentaenoic acid (EPA), gamma-linolenic acid (GLA) and alpha-linolenic acid (ALA). However, this was not the case when combining these acids at physiological concentrations. A slight increase in cell death was only obtained with three combinations of ALA, namely with AA, OA, or GLA. Other combinations with ALA, such as with LA or EPA, had respectively no effect on cell number or increased the cell number by causing less cells to die. Other PUFAs combinations tested, did not show the three groups mentioned with ALA, but only the last two types, namely, no effect, or a decrease in the amount of cell death. The latter might mean that the FA combination had stimulated the cells, since a decrease in the amount of dead cells was observed. Therefore, it is concluded that the characteristics of combined FAs may differ from single FAs, which may explain some controversies in the literature and in response to treatments.

Two roles for caveolae in the cardiac myocyte?

The presence of caveolae in many cell types including heart myocytes is well established. It is hypothesized that caveolae may play a role in the storing of excess Ca2+ and may be instrumental in Ca2+ transients during contraction and relaxation in pathological conditions. Furthermore, the presence of substances in caveolae and in their membranes may imply a role in the importing and exporting of key molecules under physiological and pathological conditions. Secretory activity is also suggested by an electron micrograph of rat heart muscle.

Does urokinase play a role in renal stone formation?

Renal stone formation is a complex multifactorial disease, and it is believed that the initial step in the pathogenesis of urolithiasis must be the precipitation of an organic matrix of mucoproteins followed by precipitation of minerals onto this matrix. An important factor in this process may be the activity and/or concentration of the urinary enzyme, urokinase, which would affect the level of urinary mucoproteins such as uromucoid. In support of this hypothesis, ELISA studies were conducted to investigate the urokinase concentrations in urine obtained from males (22-60 years) with and without renal stones. These results showed a significant decrease in urinary urokinase concentration of renal stone patients which, once again, underlines the possible involvement of urokinase in renal stone formation. Therefore, it seems logical to conclude that urokinase may play an integral role in this multifactorial disease.

Are recommendations from carcinoma of the cervix Patterns of Care Studies (PCS) in the United States of America (USA) applicable to centers in developing countries?

PURPOSE: To compare patient demographics, treatment resources, practice patterns, and outcome results for squamous cell carcinoma of the uterine cervix (SCC) between the 1978 and 1983 Patterns of Care studies (PCS) in the United States of America (USA) and a nonacademic center within a developing country. METHOD AND MATERIALS: Patient details (race, age, stage, and number per year), treatment used, and treatment outcome were retrieved from the charts of the 1160 cases registered at this center with SCC of the cervix between 1976 and 1985. Demographic variables and Kaplan-Meier survival estimates were calculated and compared with results from published PCS reviews. RESULTS: There is a significant difference in the racial group presentation of cervix cancer at this center compared with the PCS reviews (p < 0.005), and median ages are significantly lower at this center (t = p < 0.001). The proportion of patients with Stage III or more was significantly higher at this center than the PCS centers (24 vs. 47%, p < 0.001). There were also vast differences in facility resources. Fewer cases at this center underwent intracavitary insertions than at PCS centers. Mean Point A doses were significantly reduced for this center compared with the PCS reviews. Kaplan-Meier estimates were similar for Stage I and II in PCS centers and this center, but were inferior for this center in Stage III patients (p < 0.05 for OS and p < 0.01 for LC). Late morbidity rates were similar for both PCS centers and this center. CONCLUSION: PCS recommendations may be applicable to nonacademic centers within developing countries, if the latter use staging techniques that are consistent with the PCS staging guidelines.

Geotrichum candidum P-5 produces an intracellular serine protease resembling chymotrypsin.

A wide range of intra- and extracellular microbial proteases has been studied and characterized. These enzymes are mostly extracellular and in some cases they may resemble 'classical' serine proteases. As part of a programme in which the lipase and protease activities of the fungus Geotrichum candidum are being studied, an intracellular protease with an apparent chymotrypsin-like specificity was detected. The serine protease was isolated from biomass using ion-exchange and exclusion chromatography. Kinetic characterization was done using a series of synthetic substrates and inhibitors. Aprotinin-sepharose affinity chromatography was used to isolate a fraction for molecular size determination on SDS-PAGE. The purified protease, which could hydrolyse haemoglobin as protein substrate, was obtained with a 30-fold purification and a yield of 44%, but it was very unstable and rapidly lost activity. The enzyme which bound to the affinity column had a single subunit mass of 278 kDa. Kinetic analysis showed a similarity with trypsin and chymotrypsin, but tending more towards chymotrypsin in that a bulky aromatic group, e.g. phenylalanine in the P1 position, was preferred. The optimum pH was in the region of 7-8.25. Inhibition patterns indicated that the enzyme was a serine protease with no metal dependence, although it was stabilized by magnesium ions. The enzyme seems to share some properties with other intra- and extracellular microbial serine proteases. The exact function of the enzymatic activity is still unclear, but it is suggested that it may be involved with intracellular protein turnover.

The possible role of sodium-potassium adenosine triphosphatase in preterm labour.

An unacceptably high incidence of preterm labour is seen in the black and coloured communities of South Africa. This hypothesis proposes that sodium-potassium adenosine triphosphatase activity plays an important role in preterm labour. The impaired activity of the sodium pump leads to increased cytosolic calcium levels, which may trigger contraction of myometrial smooth-muscle cells, resulting in preterm labour.