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Biomedical subjects

C Schultz

Publications and source records attributed to C Schultz.

At least 73 records · Page 4Linked to original sources

Neurofibrillary pathology in the human paraventricular and supraoptic nuclei.

Severe neurofibrillary changes were identified in the paraventricular and supraoptic nuclei of elderly individuals using markers for Alzheimer's disease-related intraneuronal pathology. This neurofibrillary pathology is remarkable in that the magnocellular paraventricular and supraoptic nuclei are particularly resistant to Alzheimer's disease. Moreover, the changes were observed even in non-demented controls, indicating that they develop independently of Alzheimer's disease. The alterations in the paraventricular and supraoptic nuclei were consistently accompanied by neurofibrillary changes in the mediobasal hypothalamus.

Aged↗

Nosocomial transmission of human immunodeficiency virus and subsequent transmission of multidrug-resistant tuberculosis in a healthcare worker.

A phlebotomist with nosocomially acquired human immunodeficiency virus infection developed tuberculosis 10 months after exposure to multidrug-resistant Mycobacterium tuberculosis during a nosocomial outbreak. Healthcare workers with immunosuppression are at increased risk of tuberculosis if infected and, if exposed, should be considered for preventive therapy regardless of tuberculin skin-test status.

Adult↗

[Laparoscopy-assisted colorectal surgery. Early outcome in benign and malignant diseases--a prospective study of 120 patients].

We present our results with laparoscopic-assisted colorectal surgery in 120 patients during the time from January 1993 to September 1996. The types of procedures cover almost the whole spectrum of colorectal surgery. They included hemicolectomies, signmoid resections, low anterior resections, Hartmann closures, proctocolectomies and rectopexies. 127 patients were subjected to laparoscopic operation, 7 needed conversion to open surgery (7% conversion rate). Average operation time was 145 +/- 58 min, length of postoperative stay 12 +/- 4 days. Oral food intake was started at the second day postoperatively without major problems. We observed perioperative complications in 21 cases (17%). There were 5 anastomotic leaks, 4 wound infections, 1 pneumothorax and 2 postoperative bleedings, 4 patients had clinical signs of prolonged bowel paralysis, 2 patients died as a consequence of anastomotic leaks, 2 of other reasons. In the postoperative period we saw a marked faster recovery and a lower complication rate compared to our conventionally operated patients and postoperative pain was less. In cases of malignant disease no rise in rate of recurrence was observed during follow-up (average 18 months) compared to open surgery. Until the results of long-term studies are published laparoscopic procedures should still be restricted to early tumor stages and palliative procedures.

Adult↗

A sex difference in neurodegeneration of the human hypothalamus.

The mediobasal hypothalamus (MBH) of 33 males (mean age, 77 +/- 10 years) and 31 females (mean age, 78 +/- 10.3 years) was investigated for neurofibrillary pathology associated with abnormally phosphorylated tau protein. A conspicuous pathology was identified, characterized by terminal-like processes contacting the neurohemal vasculature of the posterior median eminence and the adjacent infundibular nucleus. This pathology revealed a striking sex difference: it was identified in 79% of the males, but observed in only 6% of the females. The vessel-associated neurofibrillary lesions of the mediobasal hypothalamus develop independently of Alzheimer's disease (AD)-related neocortical pathology. The sex-dependent neurofibrillary degeneration is suggested as an explanation for an impairment in neuroendocrine function previously reported in elderly men.

Aged↗

Radiosurgery for the treatment of previously irradiated recurrent primary brain tumors and brain metastases: initial report of radiation therapy oncology group protocol (90-05).

PURPOSE: To determine the maximum acutely tolerable dose of single fraction radiosurgery in patients with recurrent previously irradiated primary brain tumors or brain metastases. METHODS AND MATERIALS: Between August 1990 and September 1993, 102 analyzable patients were entered on Radiation Therapy Oncology Group (RTOG) protocol 90-05, 38 of whom had recurrent primary brain tumors (median prior dose 60 Gy), and 64 of whom had recurrent brain metastases (median prior dose 30 Gy) < or = 40 mm in maximum diameter. Unacceptable toxicity was defined as irreversible Grade 3, any Grade 4, or Grade 5 central nervous system (CNS) toxicity according to the RTOG CNS criteria, occurring in > 20% of patients per treatment arm within 3 months of radiosurgery. RESULTS: Patients were initially entered onto one of three treatment arms according to the maximum diameter of the recurrent lesion. Twelve to 22 patients were entered on each arm. The dose levels were: arm 1, < or = 20 mm, 18 Gy; arm 2, 21-30 mm, 15 Gy; and arm 3, 31-40 mm, 12 Gy. Subsequently, doses were escalated as follows: arm 4, < or = 20mm, 21 Gy; arm 5, 21-30 mm 18 Gy; and arm 6, 31-40 mm, 15 Gy. Unacceptable acute toxicity secondary to cerebral edema occurred in 0, 7 and 5% of patients on Arms 1, 2 and 3, respectively, and in no patients on arms 4, 5, or 6. Multivariate analysis revealed that tumor volume > or = 8200 mm(3) and a ratio of maximum dose to prescription dose (MD/PD) > or = 2 were significantly associated unacceptable toxicity. Of 15 patients with both tumor volume > or = 8200 mm(3) and MD/PD > or = 2, unacceptable toxicity occurred in 2 of 4 treated with a single isocenter and 1 of 11 treated with multiple isocenters. Subsequently, operation for symptomatic radionecrosis was required in 6% of patients. CONCLUSION: We found that the incidence of acute toxicity was acceptable at 0-7% in patients with recurrent, previously irradiated primary brain tumors or brain metastases < or = 40 mm in maximum diameter treated according to the protocol described.

Adult↗

Thermally induced hydrogen exchange processes in small proteins as seen by FTIR spectroscopy.

Fourier-transform infrared (FTIR) spectroscopy has been used to study the thermally induced exchange characteristics of those backbone amide protons which persist H-D exchange at ambient conditions in ribonuclease A, in wild type ribonuclease T1 and some of its variants, and in the histone-like protein HBsu. The H-D exchange processes were induced by increasing the thermal energy of the protein solutions in two ways: (i) by linearly increasing the temperature, and (ii) by a temperature jump. To trace the H-D exchange in the proteins, various infrared absorption bands known to be sensitive to H-D exchange were used as specific monitors. Characteristic H-D exchange curves were obtained from which the endpoints (TH/D) of H-D exchange could be determined. The H-D exchange curves, the TH/D-values and the phase transition temperatures Tm were used to estimate the structural flexibility and stability of the given proteins. It is suggested that time-resolved FTIR spectroscopy can be used to determine global stability parameters of proteins.

Amides↗

Preirradiation chemotherapy with cyclophosphamide, doxorubicin, vincristine, and dexamethasone for primary CNS lymphomas: initial report of radiation therapy oncology group protocol 88-06.

PURPOSE: This study was a prospective phase I/II trial performed by the Radiation Therapy Oncology Group (RTOG) to test the tolerance and efficacy of preirradiation cyclophosphamide, doxorubicin, vincristine, and dexamethasone (CHOD) chemotherapy followed by large-volume, high-dose brain radiation therapy (RT) for patients with primary CNS lymphoma (PCNSL). PATIENTS AND METHODS: Fifty-four (52 assessable) human immunodeficiency virus (HIV)-negative patients with PCNSL were entered on study and received two (n = 20) or three (n = 32) cycles of CHOD (six patients with positive CSF cytology received intrathecal methotrexate in addition to CHOD). Whole-brain RT to 41.4 Gy and tumor boost to 18 Gy (total dose, 59.4 Gy) followed chemotherapy. RESULTS: As of July 1994, with a minimum potential follow-up time of 20 months, 12 of 52 assessable patients remain alive without evidence of progression. The median survival time for the entire group is 16.1 months, with a 2-year survival rate of 42%. By univariate analysis, patient age was found to be a significant prognostic factor with respect to survival (P = .005) in favor of age less than 60 years. Karnofsky performance status (KPS) was of borderline significance (P = .057). Survival for patients treated on RTOG 88-06 was compared with that of patients treated on RTOG 83-15, which tested RT alone. No difference in overall survival was found (P = .53). Grade 4 neutropenia developed in 29 of 51 patients during chemotherapy. There were two deaths during chemotherapy: one as a result of sepsis and one of a pulmonary embolus. The worst toxicity during RT was < or = grade 2 in 50 of 52 patients. CONCLUSION: Preirradiation CHOD chemotherapy does not significantly improve survival over RT alone for patients with PCNSL. Age remains a powerful prognostic factor independent of therapy and must be considered in testing alternative combined approaches.

Antineoplastic Combined Chemotherapy Protocols↗

[Peripheral neuroectodermal tumor of the thoracic wall. Experiences with surgical treatment].

The peripheral neuroectodermal tumor (PNET) is seen nowadays as a more specified form of Ewing's Sarcoma with a worse prognosis. We report our experiences of three children (10-14 years old) with PNET of the right thoracic wall, all treated surgically within 1 year. Complete local resection-the main aspect of PNET therapie-of the initially voluminous tumors was not difficult due to chemotherapy and radiotherapy for 5 months prior to surgery.

Adolescent↗

The critical region in the cytoplasmic domain of human IL-4 receptor for induction of IgE synthesis.

To examine the region critical for differentiation in the human IL-4 receptor (hIL-4R), we transfected the Abelson murine leukemia virus (A-MuLV)-transformed murine pre-B cell line A20 with plasmid DNA encoding the hIL-4R. Transfectants expressed high affinity hIL-4Rs on the cell surface. Treatment with LPS and hIL-4 induced germline C epsilon transcripts in hIL-4R expressing A20 cells. Several hIL-4R mutant plasmids were then transfected into A20 cells and the transfectants were examined for hIL-4R expression and the ability to induce germline C epsilon transcripts upon stimulation with LPS and hIL-4. Although all A20 transfectants tested expressed the high-affinity hIL-4R, A20 transfectants expressing the mutant hIL-4R, which contains only 8 amino acids in the cytoplasmic domain, did not respond to LPS and hIL-4 with germline C epsilon transcripts. In addition, A20 transfectants expressing an internally deleted hIL-4R, in which the deleted region has been identified as the critical region for growth signal transduction in the previous study, failed to induce germline C epsilon transcripts with LPS and hIL-4. These results indicate that the critical region for the differentiation signal in the hIL-4R is identical to that for the growth signal, suggesting that IL-4 may share, at least partly, a common signal pathway for both growth and differentiation.

Animals↗

Cross-talk between calcium and cAMP-dependent intracellular signaling pathways. Implications for synergistic secretion in T84 colonic epithelial cells and rat pancreatic acinar cells.

Treatment of various cells with combinations of agents that increase either cAMP or cytosolic calcium can lead to synergistic responses. This study examined interactions, or cross-talk, between these two intracellular messengers and its implication for signaling in two secretory cell types, T84 human colonic epithelial cells and rat pancreatic acinar cells. T84 cell chloride secretion was measured in Ussing chambers. Acinar cell activation was monitored as amylase secretion. Cytosolic calcium was assessed via fura-2 microfluorimetry. A cell-permeant analogue of cAMP synergistically enhanced secretory responses to calcium-mobilizing hormones in both cell types, but paradoxically reduced overall calcium mobilization. The reduction in calcium mobilization could be attributed to an inhibition of calcium influx in T84 cells, although a different mechanism likely operates in acinar cells. The effects of the cAMP analogue were reproduced by other agents that increase cAMP. Furthermore, econazole, an inhibitor of calcium influx, potentiated secretory responses to calcium-dependent stimulation in T84 cells without itself inducing secretion. We conclude that there is cross-talk between calcium and cAMP-dependent signaling pathways at the level of second messenger generation in two secretory cell types. This cross-talk appears to regulate the extent of secretory responses.

Amylases↗

[Laparoscopic interventions in acute and chronic diverticulitis].

UNLABELLED: Since the beginning of 1993 until May 1994 in our hospital 25 patients were operated upon for diverticular disease. 16 patients required a laparoscopic assisted elective one-stage resection. One laparoscopic Hartmann's procedure was performed on account of a free perforation. 4 patients underwent laparoscopic reconstruction of the intestinal continuity after an Hartmann's resection. In 4 cases it was necessary to change to the conventional procedure. TECHNIQUE: the patient is placed in dorso-sacral position (modified lithotomy position) in order to allow transanal colonic access. 4 trocars are necessary. The linear stapler is used to transsect the sigmoid colon and to dissect the entire mesentery. The left lateral trocar incision is enlarged to remove the specimen. The intracorporeal double staple anastomosis is created by a circular stapler. RESULTS: there were two wound infections, one postoperative bleeding and one small anastomotic leak. After the operation we observed all advantages of the laparoscopic procedure in form of less pain, earlier beginning of bowel movements, faster return to full diet and earlier hospital discharge. These positive results combined with the possibility of a standardized procedure encourage us to continue laparoscopic sigmoidectomy.

Acute Disease↗

Nigral and extranigral pathology in Parkinson's disease.

This article reviews data on the internal organization, neuronal types, and interconnections of limbic and motor components of the human brain, and the specific lesions which a few of them undergo during the course of Parkinson's disease (neuronal loss associated with the development of Lewy bodies and Lewy neurites). The severe involvement of nigral neuromelanin-laden projection cells has received particular attention during the past decades. This lesion interferes with normal function of the striatum and probably contributes to many of the motor dysfunctions characteristically occurring in Parkinson's disease. The similarly severe involvement of several areas and nuclei outside of the substantia nigra has often escaped notice. However, the pathology of Parkinson's disease cannot be completely described unless changes in these extranigral areas are taken into account. Interpretation of the characteristic lesional pattern is facilitated by combining schemata of both the limbic and motor systems. This approach reveals a key role by the amygdala and related structures in extranigral pathology. Severe lesions occur in the central amygdaloid nucleus, in nuclei projecting to the cerebral cortex in a non-specific manner, and in nuclei regulating endocrine and autonomic functions. It is suggested that extranigral lesions contribute to the development of behavioral changes and autonomic dysfunction.

Amygdala↗

Long-term uncoupling of chloride secretion from intracellular calcium levels by Ins(3,4,5,6)P4.

Osmoregulation, inhibitory neurotransmission and pH balance depend on chloride ion (Cl-) flux. In intestinal epithelial cells, apical Cl- channels control salt and fluid secretion and are, in turn, regulated by agonists acting through cyclic nucleotides and internal calcium ion concentration ([Ca2+]i). Recently, we found that muscarinic pretreatment prevents [Ca2+]i increases from eliciting Cl- secretion in T84 colonic epithelial cells. By studying concomitant inositol phosphate metabolism, we have now identified D-myo-inositol 3,4,5,6-tetrakisphosphate (Ins(3,4,5,6)P4), as the inositol phosphate most likely to mediate this uncoupling. A novel, membrane-permeant ester prepared by total synthesis delivers Ins(3,4,5,6)P4 intracellularly and confirms that this emerging messenger does inhibit Cl- flux resulting from thapsigargin- or histamine-induced [Ca2+]i elevations.

Atropine↗