Neoadjuvant chemotherapy in invasive bladder cancer: the evolving role of surgery

The role of an operation in patients receiving neoadjuvant chemotherapy for clinically localized but invasive transitional cell carcinoma of the bladder currently is evolving. An operation is essential for case selection and evaluation of local response but it also contributes to bladder preservation and survival. The procedure that is necessary to select for and assess response to chemotherapy may itself alter the actual or proceed to evolution of invasive bladder cancer. Neoadjuvant chemotherapy is a reasonable therapeutic strategy in selected patients but it remains to be seen whether the results will prove to be superior to those achieved with standard endoscopic and open operations.     

125iodine reimplantation for locally progressive prostatic carcinoma

We treated 13 patients with a second 125iodine implant for local recurrence of prostatic carcinoma. All patients had biopsy proved palpable recurrence without evidence of distant metastases. Full doses of irradiation were used (median matched peripheral dose 170 Gy.). Six patients had complete regression of palpable recurrence, 2 had partial regression, 2 had no apparent response and 3 were unevaluable for local response. Actuarial freedom from local disease progression at 5 years was 51%. Despite a relatively high rate of local disease control the actuarial rate of distant metastases reached 100% at 6 years after reimplantation. There were 2 severe rectal complications and 4 instances of mild to moderate urinary incontinence among the 13 patients. Local regression of recurrent prostatic carcinoma may be achieved with 125iodine reimplantation but most patients still had distant metastases.     

Cadmium Mobilization by Monoaralkyl- and Monoalkyl Esters of meso-2,3-Dimercaptosuccinic Acid and by a Dithiocarbamate

Syntheses and relative cadmium mobilizing properties are described for three new monoaralkyl esters (HOOCCH(SH)CH(SH)COOR, where R = phenylethyl ((CH₂)₂C₆H₅), MPhEDMS; R = 3-phenylpropyl ((CH₂)₃C₆H₅), MPhPDMS; and R = 2-phenoxyethyl ((CH₂)₂OC₆H₅), MPhOEDMS) of meso-2,3-dimercaptusuccinic acid. These were prepared by the reaction of the corresponding alcohol with meso-2,3-dimercaptosuccinic acid (DMSA) in aqueous HCl. When administered intraperitoneally to cadmium-loaded mice at 0.50 mmol/kg/day for four consecutive days, all induced significant reductions in the whole body cadmium levels. MPhEDMS, 60%; MPhPDMS, 66%; and MPhOEDMS, 58% in comparison with control levels. At the same dosage monoisoamyl meso-2,3-dimercaptosuccinate (Mi-ADMS) and a dithiocarbamate, sodium N-benzyl-4-O-(β-D-galactopyranosyl)-d -glucamine-N-carbodithioate (BLDTC) induced reductions of 65% and 57%, respectively. Hepatic and renal cadmium were also depleted significantly, while brain cadmium levels were unchanged. These compounds induced a significant reduction in the cadmium levels of the spleen, and one, MPhOEDMS, produced a 10% decrease in pancreatic cadmium. The manner in which the later injections removed smaller fractions of the total body cadmium is consistent with a bodily distribution of these compounds by which they are concentrated primarily in the kidneys and the liver, with much smaller amounts reaching other organs. It is proposed that these compounds enter renal and hepatic cells through an anion transport system.     

Distribution of retroperitoneal metastases after chemotherapy in patients with nonseminomatous germ cell tumors.

For patients with advanced nonseminomatous germ cell tumors a retroperitoneal lymph node dissection is routinely performed following chemotherapy if the serum tumor markers have returned to normal. Bilateral retroperitoneal lymph node dissection has been recommended because metastatic deposits may be widespread. The aim of this study was to describe the distribution of retroperitoneal metastases following chemotherapy in patients with nonseminomatous germ cell tumor and determine if the extent of the retroperitoneal lymph node dissection can be modified. We studied 113 patients who had initially bulky retroperitoneal disease and underwent retroperitoneal lymph node dissection following chemotherapy. For the purposes of this study teratoma and malignant germ cell tumor are referred to as tumor. The most common location of tumor was the para-aortic area (91%) in patients with a left primary tumor and the interaortocaval area (78%) in those with a right tumor. Tumor was located outside the boundaries of a modified retroperitoneal lymph node dissection in 14 of the 60 patients with residual disease but the tumor was present within a palpable mass in 6 of these 14 patients. If the residual mass was removed and a modified retroperitoneal lymph node dissection was performed only 9 of the 113 patients (8%) would have tumor left in the retroperitoneum. For a select group of patients with advanced nonseminomatous germ cell tumor treated with chemotherapy, resection of the residual mass combined with modified retroperitoneal lymph node dissection is appropriate.     

Interhemispheric and ipsilateral connections in Parkinson's disease: relation to mirror movements.

Mirror movements (MM) occur in early, asymmetric Parkinson's disease (PD). To examine the pathophysiology of MM in PD, we studied 13 PD patients with MM (PD-MM), 7 PD patients without MM (PD-NM), and 14 normal subjects. Cross-correlogram did not detect common synaptic input to motoneuron pools innervating homologous hand muscles in PD-MM patients. Transcranial magnetic stimulation studies showed no significant difference in ipsilateral motor-evoked potentials between PD-MM patients and normal subjects. The MM side of PD-MM patients showed a slower increase in ipsilateral silent period area with higher level of muscle contraction than the non-MM side and normal subjects. There was less interhemispheric inhibition (IHI) at long interstimulus intervals of 20 to 50 ms in PD-MM than PD-NM. IHI reduced short interval intracortical inhibition in normal subjects and PD-NM, but not in PD-MM. IHI significantly increased intracortical facilitation in PD-MM and PD-NM patients, but not in normal subjects. Our results suggest that MM in PD is due to activation of the contralateral motor cortex. PD-MM patients had reduced transcallosal inhibitory effects on cortical output neurons and on intracortical inhibitory circuits compared to PD-NM patients and controls. These deficits in transcallosal inhibition may contribute to MM in PD patients.     

Comparison of standard most probable number method with three alternate tests for detection of bacteriological water quality indicators

The standard most probable number (MPN) method for the detection of total and fecal coliforms was compared with three simple microbial tests: H₂S paper strip test, Presence-absence (P-A) test for coliforms using MacConkey broth (PA-TC), and P-A test for fecal streptococci using KF streptococcal broth (PA-FS) in 187 samples of water from three districts of Indian state of Jammu and Kashmir: Doda, Udhampur, and Jammu. All three tests were comparable with the standard MPN method. However, the PA-FS and H₂S tests were found more sensitive in the detection of indicator organisms. Four hundred and fifty eight cultures obtained from positive tests were identified in order to evaluate the specificities of tests used in detection of coliform indicators. The low incidence of recovery of Escherichia coli (16–34%) for the standard MPN method places doubt on the validity of its application in tropical areas. In view of this, the need for relaxed standards of water quality in tropical areas is discussed. From the results reported here it appears that the combination of the PA-FS and H₂S test could be used as a suitable multiple test to assess the microbiological quality of drinking water in India and other tropical countries. © by John Wiley & Sons, Inc.     

5-HT1B Receptor Polymorphism and Clinical Response to Sumatriptan

The 5-HT₁ receptor agonist, sumatriptan, is highly effective in the treatment of migraine. Some patients, however, do not respond or experience recurrence of the headache. In addition, some patients report chest symptoms after sumatriptan. We investigated whether these different responses could be attributed to genetic diversity of the 5-HT_1B receptor, which most likely mediates the therapeutic action and the coronary side effects of sumatriptan. Allele frequencies of two polymorphisms in the 5-HT_1B receptor gene ( G861C and T-261G ) were investigated in migraine patients with consistently good response to sumatriptan (n=14), with no response (n=12), with recurrence of the headache (n=12), with chest symptoms (n=13), and in patients without chest symptoms (n=27). Allele frequencies (G:0.74; C:0.26 at nt 861 and T:0.39; G:0.61 at nt -261) did not differ between patient groups, indicating that genetic diversity of the 5-HT_1B receptor does not seem to be involved in the different clinical responses to sumatriptan.     

18F]-Dopa positron emission tomography imaging in early-stage, non-parkin juvenile parkinsonism.

There are few reports of positron emission tomography (PET) in juvenile parkinsonism (JP). We report on the results of (18)F-6-fluoro-L-dopa (FD) PET in a 14-year-old patient with JP of 5 years duration associated with atypical features. This is the youngest subject to be investigated to date. There was a severe asymmetric reduction in striatal FD uptake, with a rostrocaudal gradient in the putamen similar to that seen in adult-onset idiopathic parkinsonism. Extensive DNA analysis in this patient did not show mutations in the parkin gene.