Search PubMed⌕ Search

Biomedical subjects

C Jacobs

Publications and source records attributed to C Jacobs.

At least 217 records · Page 12Linked to original sources
PubMed1991

Chemotherapy for recurrent and metastatic head and neck cancer.

At the present time, the treatment of recurrent and metastatic head and neck squamous and salivary gland cancers with chemotherapy is palliative. Pain relief, improvement in functional parameters, and improved survival are important goals. Although survival benefits are small, palliation can be significant. For squamous cancers, the median duration of response to chemotherapy is 2 to 4 months, and overall survival is about 6 months. Responses can be achieved with acceptable toxicity for good palliation in approximately 30% of patients treated with the standard regimens. Although more intensive chemotherapy regimens often result in higher response rates in pilot trials, they do not offer significant gains in effectiveness or survival. In salivary gland malignancies, results are substantially better, but this may only reflect the different natural history of this heterogeneous group of tumors. A small number of patients will have excellent and very durable responses to chemotherapy. Unfortunately, at this time we are unable to select these patients or determine which regimen will produce this desired result. The optimal use of currently available drugs is in the process of refinement. The timing of palliative chemotherapy represents a major challenge to oncologists and patients. Chemotherapy may in the future have a role in the cure of patients with recurrent disease, but innovative therapy, combined modality approaches, and new drug development will all need to be investigated. We look forward toward a new understanding of tumor biology and the development of agents that may substantially improve the control of these tumors.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1991

[Can cisplatin renal toxicity be prevented?].

Cis diamminedichloroplatinum (CDDP) is a widely used anticancer agent particularly effective in the treatment of solid tumors. Dose limiting toxicity of CDDP was shown to be renal. Numerous methods to reduce this nephrotoxicity have been proposed. Hydration remains the best protection against acute CDDP nephrotoxicity in both the clinical and experimental setting. In man, no controlled studies have demonstrated the efficacy of furosemide and mannitol in the reduction of the CDDP renal toxicity. Studies have shown, however, that sodium thiosulfate offers some nephroprotection. To date, no controlled studies have demonstrated any benefit in the use of calcium channel blockers on CDDP renal toxicity in man. New drugs such as carboplatin have recently been introduced that theoretically have less renal toxicity, but evidence to support these claims are lacking. CDDP nephro protection remains a problem of current clinical interest and has yet not to be totally resolved.

Calcium Channel Blockers↗
PubMed1991

Renal vasoconstriction after low and high osmolar contrast agents in ischemic and non ischemic canine kidney.

We have assessed the effect of contrast media on renal blood flow before and after inducing renal ischemia. Diatrizoate, iopamidol and ioxaglate were injected within 15 seconds at 20 min intervals, at the dose of 1 ml/kg during a control period and 15 min after applying an aortic clamp to reduce the renal perfusion pressure to 70 mmHg. During the control period iopamidol, ioxaglate (17 +/- 13%) and diatrizoate (16 +/- 2%) induced a comparable decrease in renal blood flow (RBF). During the ischemic period the effects of diatrizoate on renal hemodynamic were dramatically enhanced. Ioxaglate andiopamidol induced a 20 +/- 12 and a 32 +/- 9% decrease in RBF at 1 minute, respectively. Iopamidol induced an increase in renal vascular resistance (RVR) from 0.8 +/- 0.08 to 1.46 +/- 0.26 mmHg min/ml (p less than 0.05). Ioxaglate induced an increase in RVR from 0.8 +/- 0.09 to 1.36 +/- 0.38 (p less than 0.05). Diatrizoate induced a 77 +/- 10% decrease in RBF and a maximum increase in RVR at 1 minute from 0.9 +/- 0.09 to 26 +/- 12 mmHg min/ml. There was still a 36 +/- 14% and a 23 +/- 13% decrease in RBF 10 and 20 min after diatrizoate administration. These changes were significantly higher than those observed with all contrast media during the control period and low osmolar contrast media during the ischemic period. We have thus shown that ischemia potentiates the renal vascular effect of contrast media.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Kidney Injury↗
PubMed1990

[Drug-induced interstitial nephropathy with nephrotic syndrome].

A new syndrome is which immunoallergic interstitial nephropathy is associated with nephrotic syndrome has recently been described. The interstitial nephropathy is usually due to the consumption of non steroidal anti-inflammatory drugs, and it is characterized by interstitial lesions associated with minimal glomerular lesions. The typical clinical complex includes nephrotic syndrome, renal impairment, eosinophilia, microscopic haematuria, leucocyturia and, more rarely, clinical signs of hypersensitivity. The outcome is favourable as a rule, with recovery of the renal function ad integrum and complete recession of the nephrotic syndrome. The pathogenesis of the syndrome is no entirely clear, but it probably implies a delayed hypersensitivity reaction. Treatment consists of withdrawing the responsible drug(s) and applying medical intensive care methods. Whether or not corticosteroids influence the rapidity and quality of recovery remains uncertain.

Acute Disease↗
PubMed1990

The internist in the management of head and neck cancer.

The general internist has an important role in the management of head and neck squamous cell cancers. This heterogeneous group of cancers must be accurately diagnosed and staged before planning treatment. Curability is directly related to stage at presentation and, because most patients with such cancers present to internists first, these physicians must be familiar with presenting symptoms and must be suspicious enough to refer patients with symptoms for appropriate evaluation. The work-up of patients with suspected unknown primary cancer presenting as adenopathy is detailed, and the physician is cautioned not to immediately proceed to open biopsy. As many as 10% of such primary cancers remain undetected, although, with proper therapy, the 5-year survival rate for squamous cell cancer of the head and neck is 60%. Those patients cured of head and neck cancer still face significant psychosocial and medical problems, including hypothyroidism, xerostomia, and a 20% rate of second primary cancer. Head and neck cancer is highly preventable; 75% of cases are related to tobacco and alcohol use. Smokeless tobacco has gained popularity among young Americans and is associated with an increased incidence of head and neck cancer at several sites. Education is crucial, and internists must seek strategies to stop patients from using tobacco products. Other etiologic factors include industrial carcinogens, Epstein-Barr virus, and diet. Retrospective serologic and dietary recall studies of vitamin A suggest an etiologic role of diet; vitamin A analogs have been tested in preneoplastic lesions. To reduce mortality from head and neck cancers, the general internist must play a central role in prevention and early detection.

Carcinoma, Squamous Cell↗
PubMed1990

The clinical presentation of Wilms' tumour in black children.

The pattern of presentation of black children with Wilms' tumour is reported. Differences between children from rural and urban areas are emphasised. Factors which distinguish these groups from First-World population groups are highlighted and the possible implications for treatment design stressed.

Age Factors↗
PubMed1990

IL-1 beta modulation of spontaneous autoimmune diabetes and thyroiditis in the BB rat.

Long term effects of in vivo treatment with human rIL-1 beta on diabetogenesis and thyroid disease were determined in the Biobreeding rat. Administration of high dose (10 micrograms/kg) IL-1 beta accelerated the onset of insulin-dependent diabetes mellitus compared to saline-injected controls. High dose treatment resulted in goiter development, pronounced LT, reduced serum T4 levels, and overall growth reduction. In contrast, low dose IL-1 beta (0.5 microgram/kg) administration significantly reduced the frequency of insulin-dependent diabetes mellitus (48%) compared to placebo (86%) and high dose IL-1 beta (93%) treatment groups. Rats protected by low dose IL-1 beta had unaffected growth rates and minimal to no pancreatic and thyroid pathology. Our results demonstrate that exogenous administration of IL-1 beta modulates Biobreeding rat idiopathic autoimmune diabetes and thyroid disease in a dose-dependent manner.

Animals↗
PubMed1990

Cicletanine does not affect plasma atrial natriuretic peptide concentration in healthy subjects.

The effect of 50 and 150 mg cicletanine, a new vasodilator antihypertensive, on plasma atrial natriuretic peptide (ANP), cyclic GMP and antidiuretic hormone has been investigated at rest and during standardized exercise, in a double blind cross over study in healthy subjects. Exercise significantly increased in plasma ANP, cyclic GMP and antidiuretic hormone concentrations, and cicletanine did not affect any of them either at rest or during exercise. Since the alpha-1 adrenoceptor blocker prazosine decreases, beta-adrenoceptor blockers increase and the vasodilator cicletanine does not alter the plasma ANP response to exercise, it is suggested that adrenergic receptors may be directly involved in the regulation of ANP secretion.

Administration, Oral↗
PubMed1990

Renal effects of S10036 in man.

The renal hemodynamic and tubular effects of S10036 (fotemustine) were evaluated in seven patients with advanced malignancy. Initial evaluation carried out prior to treatment and repeated 1 day after the first fotemustine infusion and 7 days after the second included clinical, haematological parameters, liver-function tests, and determination of the glomerular filtration rate, renal blood flow and enzymuria. The glomerular filtration rate was 108 +/- 3.7 ml/min before treatment and remained stable after the first (117 +/- 5 ml/min) and second (124 +/- 6 ml/min) fotemustine infusions. Renal blood flow and urinary beta 2-microglobulin and N'-acetylglucosaminidase excretion were also not modified by fotemustine administration. We conclude that fotemustine does not acutely alter renal haemodynamics, nor does it have direct tubular toxicity.

Acetylglucosaminidase↗
PubMed1990

A role for adenosine calcium and ischemia in radiocontrast-induced intrarenal vasoconstriction.

These studies were designed to test the hypothesis that adenosine and calcium are important in mediating radiocontrast-media-associated reduction in renal blood flow (RBF) in the dog. Intravenous verapamil (V) and diltiazem (DTZ) infusion significantly attenuated the magnitude of the vasoconstrictor response observed after each intrarenal contrast media (CM) injection. (First injection: -47 +/- 8% control vs. -14 +/- 3% V, p less than 0.03; -38 +/- 4% control vs. -19 +/- 3% DTZ, p less than 0.02. Second injection: -33 +/- 6% control vs. -12 +/- 1% V, p less than 0.03; -32 +/- 5% control vs. -17 +/- 2% DTZ, p less than 0.03. Third injection: -32 +/- 6% control vs. -11 +/- 5% V, p less than 0.03; -38 +/- 5% control vs. -10 +/- 5% DTZ, p less than 0.02). Furthermore, V and DTZ almost completely abolished the increase in renal vascular resistance (RVR) induced by each CM administration. Theophylline also significantly attenuated the magnitude of the vasoconstrictor response observed after CM injection (first injection: -31 +/- 3% control vs. -12 +/- 3% theophylline, p less than 0.05; second injection: -26 +/- 3% control vs. -12 +/- 3% theophylline, p less than 0.03). Similarly, theophylline blunted the increase in RVR induced by CM injection. In addition, theophylline inhibited exogenous adenosine-induced decrease in RBF (-61 +/- 10% and -26 +/- 1% decrease in RBF without and with theophylline, respectively). In contrast, dipyridamole significantly enhanced the vasoconstriction induced by CM (first injection: 25 +/- 3% control vs. 49 +/- 4% dipyridamole; second injection: 31 +/- 3% control vs. 48 +/- 4% dipyridamole p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Kidney Injury↗
PubMed1990

Renal effects of radiocontrast agents in rats: a new model of acute renal failure.

The objectives of this study were first to develop a reproducible and reversible model of acute renal failure following contrast medium infusion in the rat; second to use that method to compare the nephrotoxicity of low- and high-osmolar contrast agents. Contrast media or saline were perfused in the aorta while a clamp was applied on the aorta just above the renal artery. Three minutes of renal ischemia with or without infusion of isotonic saline induced no change in serum creatinine and a slight and transient decrease in creatinine clearance at 24 h. Urinary N-acetyl glucosaminidase (NAG) excretion was not modified in this control group. All 17 kidneys which were examined were normal. 2,100 mosm/kg hypertonic saline induced a significant increase in serum creatinine and a significant decrease in creatinine clearance (from 1.8 +/- 0.1 to 0.8 +/- 0.1 and 1.0 +/- 0.2 ml/min at 24 and 48 h, respectively). Urinary NAG excretion increased from 23 +/- 18 to 48 +/- 20 and 8 +/- 4 mumol h-1/mmol creatinine at 24 and 48 h, respectively (p less than 0.05). Histologic analysis of 5 kidneys revealed acute tubular necrosis (n = 3) and no histologic abnormalities (n = 2). Diatrizoate induced an acute and reversible renal failure. Creatinine clearance decreased from 1.6 +/- 0.1 to 0.4 +/- 0.1 and 0.8 +/- 0.1 ml/min at 24 and 48 h, respectively (p less than 0.01). Urinary NAG excretion increased also significantly from 43 +/- 9 to 352 +/- 79 and 64 +/- 23 mumol h-1/mmol creatinine at 24 and 48 h, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylglucosaminidase↗
PubMed1990

Efficacy of adjuvant chemotherapy for patients with resectable head and neck cancer: a subset analysis of the Head and Neck Contracts Program.

To evaluate the efficacy of adjuvant chemotherapy for patients with advanced head and neck squamous cancer, the Head and Neck Contracts Program conducted a three-arm study comparing standard surgery and radiation, induction chemotherapy (cisplatin and bleomycin) plus standard therapy, and induction chemotherapy plus standard therapy followed by maintenance cisplatin for 6 months. As previously reported, this trial of 462 patients demonstrated no significant difference in disease-free survival or survival, but a significantly lower metastatic rate in the maintenance arm. To determine whether particular subgroups may have benefited from adjuvant therapy, we evaluated results based on primary site, and tumor (T) and node (N) stage. Of the 192 patients with oral cavity cancer, those on the maintenance arm had a significantly improved 3-year disease-free survival (67%) compared with the standard arm (49%) or induction arm (44%) (overall P = .05). For hypopharyngeal and laryngeal cancers there was no marked overall benefit. For the 106 patients with T1 plus T2 disease, there was marginal improvement in disease-free survival for the maintenance group (72%) compared with the standard group (47%) or induction group (43%) (overall P = .09). There was no advantage for patients with T3 and T4 disease. There was superior disease-free survival for patients with N1 disease on the maintenance arm (70%) compared with the standard arm (42%) (P = .024). The same was true for disease-free survival in 109 patients with N2 disease: standard (52%), induction (30%), maintenance (84%) (overall P less than .001). There was no benefit for N3 disease. A significant survival advantage with maintenance chemotherapy was only seen for N2 disease (overall P = .04). Since head and neck cancer patients are a heterogeneous group, there may be particular sites and stages for which adjuvant chemotherapy would be advantageous, and subset analysis can help indicate directions for new trials.

Antineoplastic Combined Chemotherapy Protocols↗