Quantitative measurement of pain sensation in patients with Parkinson disease.

BACKGROUND: Pain is common in patients with Parkinson disease (PD) and can precede the diagnosis of the disease. Experimental studies and clinical evidence indicate involvement of basal ganglia and dopaminergic pathways in central pain processing. OBJECTIVE: To quantitatively assess and compare pain perception in patients with unilateral PD with and without pain and in patients with response fluctuations. METHODS: Thirty-six patients with PD (mean age, 61.8 +/- 11.2 years) with predominantly unilateral disease, 15 patients with response fluctuations (mean age, 65.3 +/- 10.4 years), and 28 age-matched healthy control subjects participated in the study. Subjective pain was assessed using the visual analog scale with von Frey filaments for tactile thresholds and contact thermode for warm sensation (WS) and heat pain thresholds (HPTs). RESULTS: Tactile and WS thresholds did not differ between patients in both patient groups and control subjects nor between sides. HPT was lower in patients with PD who experienced pain (n = 21) compared with those who did not (42.6 +/- 3.0 degrees C vs 45.6 +/- 2.8 degrees C; p < 0.01) and those who experienced pain in the more affected side (41.4 +/- 2.6 degrees C vs 43.7 +/- 3.3 degrees C; p < 0.0001). In patients with fluctuations there were no side differences in WS and HPT or between "on" and "off" periods. CONCLUSION: Endogenous pain in patients with Parkinson disease is accompanied by increased sensitivity to some painful stimuli, suggesting that basal ganglia abnormality also involves pain encoding.

Adenoviral vector-mediated insulin gene transfer in the mouse pancreas corrects streptozotocin-induced hyperglycemia.

Therapy for type 1 diabetes consists of tight blood glucose (BG) control to minimize complications. Current treatment relies on multiple insulin injections or an insulin pump placement, beta-cell or whole pancreas transplantation. All approaches have significant limitations and have led to the realization that novel treatment strategies are needed. Pancreatic acinar cells have features that make them a good target for insulin gene transfer. They are not subject to autoimmune attack, a problem with pancreas or islets transplantation, they are avidly transduced by recombinant adenoviral vectors, and capable of exporting a variety of peptides into the portal circulation. Recombinant adenoviral vectors were engineered to express either wild-type or furin-modified human insulin cDNA (AdCMVhInsM). Immunodeficient mice were made diabetic with streptozotocin and injected intrapancreatically with the vectors. BG and blood insulin levels have normalized after administration of AdCMVhInsM. Immunohistochemistry and electron microscopy showed the presence of insulin in acinar cells throughout the pancreas and localization of insulin molecules to acinar cell vesicles. The data clearly establish a relationship between intrapancreatic vector administration, decreased BG and elevated blood insulin levels. The findings support the use of pancreatic acinar cells to express and secrete insulin into the blood stream.

Proteolysis of bacteriophage lambda CII by Escherichia coli FtsH (HflB).

FtsH (HflB) is a conserved, highly specific, ATP-dependent protease for which a number of substrates are known. The enzyme participates in the phage lambda lysis-lysogeny decision by degrading the lambda CII transcriptional activator and by its response to inhibition by the lambda CIII gene product. In order to gain further insight into the mechanism of the enzymatic activity of FtsH (HflB), we identified the peptides generated following proteolysis of the phage lambda CII protein. It was found that FtsH (HflB) acts as an endopeptidase degrading CII into small peptides with limited amino acid specificity at the cleavage site. beta-Casein, an unstructured substrate, is also degraded by FtsH (HflB), suggesting that protein structure may play a minor role in determining the products of proteolysis. The majority of the peptides produced were 13 to 20 residues long.

Indications for cone biopsy: pathologic correlation.

OBJECTIVE: Our purpose was to determine the ability of different indications for cone biopsy to predict the presence of disease in the cone specimen and the utility of conization for low-grade disease. STUDY DESIGN: The records were reviewed of all patients who had an excisional cone biopsy at Queens Hospital Center between 1984 and 1995. Data were gathered regarding cytologic studies, visualization of the transformation zone, colposcopically directed biopsy, and endocervical curettage. The indications for the cone procedure were grouped as being for treatment (biopsy-proved disease) (indication A), discrepancy between cytologic and histologic diagnoses (indication B), positive endocervical curettage results (indication C), and transformation zone not fully visualized (indication D), and combinations of the above. RESULTS: Two thousand nine hundred sixty-nine records were reviewed. Of these, 604 had cone biopsies. Three hundred twenty-three of 355 (91%) cone biopsies done for indication A alone had disease on the cone specimen (defined as any grade of dysplasia or condyloma). Forty of 47 (85.1%) cone biopsies done for indication B alone had disease of the cone specimen. Forty-three of 46 (93.5%) cone biopsies done for indication C alone had disease on the cone specimen. Ninety-one cone procedures were done for a combination of indications A and D, with 87 (95.6%) showing disease on the cone specimen. Thirty-one procedures were done for a combination of indications B and D, with 25 (80.6%) showing disease on the cone specimen. Cone procedures were done on 32 women for a combination of indications C and D, and 30 (93.8%) had disease on the cone specimen. Two cone procedures were done because of the colposcopic appearance alone; one had high-grade disease on the cone specimen. Age did not help to predict the likelihood that disease would be found on the cone specimen. The data were then reanalyzed to determine the likelihood of finding high-grade disease (cervical intraepithelial neoplasia grades 2 or 3 or invasive cancer) on the cone specimen. Overall, those with preoperative high-grade cytologic or histologic characteristics (cervical intraepithelial neoplasia grades 2 or 3) were much more likely to have high-grade disease (277/371 [74.7%]) than were those with preoperative low-grade cytologic or histologic characteristics (condyloma or cervical intraepithelial neoplasia grade 1) (49/233 [21.0%]) (p < 0.001). CONCLUSION: Neither age nor the preoperative grade of disease are good discriminators of the likelihood that disease will be found on a conization specimen. However, patients who have high-grade disease on the preoperative evaluation are much more likely than those with only low-grade disease to have high-grade dysplasia or cancer on a subsequent conization.

The value of repeat Pap smear at the time of initial colposcopy.

OBJECTIVE: The objective was to determine if repeating a Pap smear at the time of an initial colposcopy has sufficient clinical benefit to justify its clinical and financial costs. METHODS: The records were reviewed of all patients who had an initial colposcopy at Queens Hospital Center between 1984 and 1995. Data were gathered regarding the referral cytology, the cytology done at the time of colposcopy, and the results of any biopsies which were taken. The terminology for cytology and histology done prior to 1989 was adjusted to the Bethesda classification system. A repeat Pap smear was defined as clinically valuable if it would have changed the patient's management, i.e., if it suggested more advanced disease than the referral Pap and that the disease was not identified on the colposcopically directed biopsy. RESULTS: Two thousand nine hundred sixty-nine records were reviewed. In 139 cases, no Pap smear was repeated at the time of colposcopy. Of the remaining 2830 women, only 1347 (47.6%) showed exact correlation between their referral Pap smear and the Pap done at the time of colposcopy. In another 1016 (35.9%), the Pap at colposcopy was within one grade of the referral Pap. In 312 women, the Pap at the time of colposcopy was a higher grade than the referral Pap. However, in 236, the higher grade of disease was detected by the colposcopically directed biopsy. Of the remaining 76 women, 58 had a normal biopsy, but their Pap at the time of colposcopy showed low-grade squamous intraepithelial lesions (44) or high-grade squamous intraepithelial lesions (HGSIL) (14). Seventeen others had a biopsy showing low-grade dysplasia while the Pap at the time of colposcopy showed HGSIL. In 1 patient, the repeat Pap showed malignant cells while the biopsy showed a high-grade lesion. Based on the triage protocols at our institution, this means that a repeat Pap at the time of colposcopy would have indicated a cone biopsy in 31 patients (1.1%) and more careful follow-up of another 44 patients (1.6%). Skipping the repeat Pap smear would not have resulted in any missed cancers. In our series of 2830 patients, the cost savings of skipping the repeat smear would have been $68,580 or $24.23 per patient. On a national level, skipping the repeat smear would save more than $24,000,000 annually. CONCLUSION: Using current triage protocols at our institution, repeating the Pap smear at the time of an initial colposcopy would have changed the management in 2.7% of patients and indicated a conization in only 1.1% of patients. It is doubtful that this justifies its cost and the potential detrimental effects on the colposcopic examination.