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Biomedical subjects

M Lind

Publications and source records attributed to M Lind.

At least 73 records · Page 4Linked to original sources
PubMed1994

Incidence, racial differences, and prognostic significance of prostate carcinomas diagnosed with obstructive symptoms.

BACKGROUND: It is unknown how often prostate carcinomas are diagnosed as a result of urinary obstructive symptoms or whether prostate carcinomas diagnosed because of obstructive symptoms have a favorable or unfavorable prognosis. It is also unknown whether racial differences in obstructive symptoms could help explain why black men with prostate carcinoma are diagnosed with more advanced stages and grades of prostate carcinoma than are white men with prostate carcinoma. METHOD: At a single Veterans Administration Medical Center, 478 consecutive cases of prostate carcinoma diagnosed between 1973 and 1985 were identified. The incidence of obstructive symptoms at diagnosis, racial differences in obstructive symptoms, and the survival of patients with and without obstructive symptoms, stratified by stage and grade, were determined. In addition, racial differences in the frequency of surgical intervention required to relieve the obstructive symptoms were determined. RESULTS: All patients diagnosed with Stage A prostate carcinoma and most (82%) patients diagnosed with Stage C prostate carcinoma had obstructive symptoms. Those diagnosed with Stage B and Stage D prostate carcinomas had with similar frequencies (53% and 55%, respectively) of obstructive symptoms. Survival, stratified by stage and grade, was similar for men with and without obstructive symptoms. The incidences of obstructive symptoms and the frequency of surgical intervention to relieve the obstructive symptoms, stage for stage, were similar for white and black men. CONCLUSION: Survival, stratified by stage and grade, is not affected adversely by obstructive symptoms. Neither racial differences in the incidence of obstructive symptoms nor the frequency with which obstructive symptoms require surgical correction explain why black men with CAP consistently are diagnosed more frequently with Stage D prostate carcinoma and less frequently with Stage A CAP than white men with CAP.

Adult↗
PubMed1994

Results of chemotherapy using ifosfamide with doxorubicin in advanced breast cancer.

Ifosfamide has single agent activity in advanced breast cancer and may potentiate the activity of doxorubicin. The combination of ifosfamide 5 g/m2 and doxorubicin 40 mg/m2 every 3 weeks for 4 cycles was used to treat 77 patients with advanced breast cancer. Fifty three patients had not received prior chemotherapy. All patients had one or more poor prognostic features, including tumor expression of epidermal growth factor receptor in 11/12 tested. The overall response rate was 74% (95% confidence intervals 62%-83%). The median survival was 9.4 months. The principal toxicities were febrile neutropenia and ifosfamide encephalopathy each in 6% of patients. A high percentage of the projected dose intensity was administered. This is a highly active combination with acceptable toxicity in advanced breast cancer, although the long term survival remains poor. Further exploration of ifosfamide in combination chemotherapy for advanced breast cancer is warranted.

Adult↗
PubMed1994

Long-term survival of stage A prostate carcinoma, atypical hyperplasia/adenosis and BPH.

Between 1972 and 1986, 134 patients with stage A carcinoma of the prostate (CAP) were diagnosed at a single Veterans Administration medical centre and followed annually by the hospital tumour registry. Seventy-four were classified as stage A1, defined as non-palpable, well-differentiated CAP, regardless of amount, found unexpectedly on transurethral resection of the prostate (TURP). Twenty-eight were classified as stage A2, defined as non-palpable, moderately or poorly differentiated CAP, regardless of amount, found unexpectedly on TURP. The remaining 32 were reclassified as atypical hyperplasia/adenosis (AH/A) rather than CAP. The survival of each group was compared with the survival of a control group from the same medical centre who had TURPs showing histologically proven benign prostatic hyperplasia (BPH). Survival and tumour progression were similar for patients with stage A1 CAP, AH/A and BPH. Furthermore, patients with stage A1 CAP, with or without therapy, had similar survivals as patients with BPH in each age group (under 65, 65-74 and over 74 years). Stage A2 CAP was associated with a significantly worse survival and more tumour progression. Within stage A1 CAP and stage A2 CAP the percentage of chips with CAP or the amount of CAP removed did not affect survival.

Adult↗
PubMed1994

Implementing a research-based protocol: an interactive approach.

Endotracheal suctioning (ETS) is a common procedure done in the critical care environment. There are many different practices related to ETS. With the proliferation of research studies about ETS, a change in practice is needed to incorporate these research findings. The authors present a creative teaching strategy that was used to implement a research-based ETS protocol.

Clinical Nursing Research↗
PubMed1993

Recombinant human interleukin-4 (rhu IL-4) administered by the intravenous and subcutaneous routes in patients with advanced cancer--a phase I toxicity study and pharmacokinetic analysis.

19 patients with advanced cancer were entered into a phase I study of recombinant human interleukin-4 (rhu IL-4). The predominant clinical side-effects included flu-like symptoms, gastrointestinal upset, lethargy and transient hypotension. In addition, there were several cases of capillary leak syndrome. 2 cases of gastrointestinal haemorrhage occurred; this was life threatening in 1 patient. The maximum tolerated dose (MTD) was 400 micrograms/m2/day. Biochemical toxicity was limited to asymptomatic elevation of liver enzymes suggesting IL-4 induced liver damage. Pharmacokinetic analysis following the intravenous bolus injection has shown that IL-4 is rapidly cleared (mean T1/2 = 19 +/- 8.7 min) from a small compartment (mean Vd = 4.9 +/- 3.68 l) probably indicating that IL-4 is retained in the systemic circulation or at most the extracellular fluid volume. 2 patients with non-Hodgkin lymphomas (NHL) showed a transient response to IL-4 whilst a third patient with NHL showed transient disease progression.

Adult↗
PubMed1993

Advanced ovarian cancer. Drug resistance, supportive care and dose intensity.

BACKGROUND: Both intrinsic and acquired drug resistance occur in ovarian cancer. Much work on in vivo or in vitro, obtained drug resistance has been done and this knowledge is presently being converted into clinical studies. MATERIALS AND METHODS: The review focuses on the detoxifying system, MDR (multidrug resistance), and supportive care in relation to dose intensity. RESULTS: In vitro models suggest that the amount of glutathione, glutathione S-transferase activity or metallothioneins could play a role in the outcome of chemotherapy treatment. The results of human tumour samples studies however do not support this idea. Expression of the cell membrane P-glycoprotein in tumour cells appears in vitro to be an important adverse prognostic factor concerning the effect of natural products. Again the results in human tumour samples vary. The supportive agent sodium thiosulphate protects against cisplatin induced nephrotoxicity, but the exact role of sulphur compounds in ameliorating the neurotoxicity is not yet established. The neuropeptide Org 2766 may be a possible neuroprotector. Hemopoietic growth factors such as GM-CSF, G-CSF and interleukin-3, protect the bone marrow to varying degrees. Autologous bone marrow transplantation induces high, but often short lasting response rates in chemotherapy resistant patients. CONCLUSIONS: More clinical studies on intervention of drug resistance and on high dose chemotherapy are needed to define the role of these strategies in ovarian cancer.

Adult↗
PubMed1993

A randomised dose intensity study in ovarian carcinoma comparing chemotherapy given at four week intervals for six cycles with half dose chemotherapy given for twelve cycles.

BACKGROUND: The importance of dose intensity has not been clearly defined in ovarian cancer and we present a prospectively randomised trial of dose intensity in patients with ovarian cancer. PATIENTS AND METHODS: Ninety-nine patients with FIGO stage Ic, II, III and IV epithelial ovarian cancer were randomised to receive cycles of standard dose cyclophosphamide (600 mg/m2) and carboplatin (300 mg/m2) alternating with adriamycin (50 mg/m2) and ifosfamide (5 G/m2) for 6 cycles at monthly intervals (49 patients) or cycles of half dose cyclophosphamide (300 mg/m2) and carboplatin (150 mg/m2) alternating with adriamycin (25 mg/m2) and ifosfamide (2.5 G/m2) for 12 cycles at monthly intervals (50 patients). Patients in each arm were well balanced for major prognostic factors. RESULTS: The combined clinical response rate (complete response and partial response) on the 6 month arm was 76% compared with 48% on the low dose intensity arm (p = 0.009). With a median follow up of 25.7 months the median survival on the low dose intensity arm is 20.9 months. The median survival point on the 6 month arm has not yet been reached. The median progression free interval on the 12 month arm was 19.8 months, the median value has not yet been reached on the standard arm. The amount of residual tumour following initial laparotomy was the only significant independent variable affecting survival (p = 0.0001). The mean received dose intensity of each drug was greater than 80% of the planned dose intensity. More patients had clinical disease progression during treatment on the low dose intensity arm (42%) when compared to the standard dose intensity arm (8%) (p = 0.0003). Fifteen patients on the standard dose arm experienced a total of 18 delays and 5 patients on the low dose arm experienced 17 delays. Nausea, vomiting and diarrhoea were similar for both standard and low dose cycles of chemotherapy with a consequent benefit for patients receiving fewer cycles even though these were of higher dose. CONCLUSIONS: The combination studied was more effective when given at the higher dose intensity and the improved response and survival was not accompanied by a significant increase in toxicity.

Adenocarcinoma↗
PubMed1993

Transforming growth factor-beta enhances fracture healing in rabbit tibiae.

The ability of exogenous Transforming Growth Factor-beta (TGF-beta) to stimulate bone formation in fracture healing was investigated. TGF-beta was continuously applied in doses of 1 and 10 micrograms/day for 6 weeks to 2 groups of adult rabbits with unilateral plated mid-tibial osteotomies. A group receiving solvent without TGF-beta served as control. Fracture healing was evaluated by mechanical tests, bone morphometry and bone densitometry. Increased maximal bending strength and callus formation were demonstrated in the groups receiving TGF-beta. TGF-beta had no effect on bending-stiffness, bone mineral content, cortical thickness or haversian canal diameter. We conclude that local application of exogenous TGF-beta may enhance fracture healing in rabbits.

Animals↗
PubMed1992

Prevalence of the Rhesus-negative phenotype in Caucasian patients with small-cell lung cancer (SCLC).

We report that the Rhesus (Rh)-negative phenotype is more prevalent in patients with small-cell lung cancer (SCLC) than in the normal Caucasian population (SCLC: 25% Rh-negative vs. 15% expected, p less than 0.0001). This finding has been validated for a Central and a Northern European population (Switzerland and UK). In contrast, the Rh-negative phenotype is no more frequent in non-small-cell lung cancer patients or in heavy smokers with coronary heart disease than in the general population. There was a normal distribution of the ABO blood group phenotype in all patients studied. Whilst the significance of this observation is unclear, we hypothesize that a genetic predisposition to the development of SCLC may be linked to a hitherto unidentified gene on chromosome 1p near the Rh locus. Our observation may perhaps allow further progress to be made in understanding genetic mechanisms of SCLC carcinogenesis.

ABO Blood-Group System↗
PubMed1992

The prognostic value of cytometric DNA analysis in early stage tongue cancer.

In spite of a small size and seemingly localised properties T1 tongue cancer does recur after surgical treatment, locally and/or in regional lymph-nodes, in 30-40% of the patients, and 50% of patients with recurrent disease die because of their cancer. If these patients could be identified by analysis of relevant parameters on the primary biopsy reflecting the biological properties of the tumours more extensive treatment regimes could be given selectively. In 47 primary biopsy specimens from patients with T1N0M0 squamous cell carcinoma of the mobile tongue the aberration in cellular DNA content was significantly higher in the group of tumours which recurred after surgical treatment compared with the non-recurrent group. Tumours in females recurred more frequently than in males. No significant correlation between recurrence and grade of histological differentiation or tumour thickness could be found. Image cytometry DNA analysis provides an objective and reproducible assessment of the nuclear DNA content which could facilitate selection of adequate treatment strategies.

Adult↗
PubMed1992

Effect of local prostaglandin E2 on periosteum and muscle in rabbits.

We assessed the target tissue for the stimulatory effect of prostaglandin E2 (PGE2) on bone formation previously observed during fracture healing. PGE2 was infused into tibial periosteal tissue in the right leg of 7 rabbits and into the anterior tibial muscle in the right leg of 7 other rabbits for 6 weeks. Solvent solution was infused into the left leg. PGE2 infusion at the periosteum caused the formation of primitive woven bone with large amounts of connective tissue; solvent infusion caused small amounts of normal periosteal bone formation. In the neighboring cortical bone, remodeling was increased after PGE2 infusion compared to solvent infusion. In the muscle, PGE2 infusion caused the formation of connective tissue with small amounts of woven bone. Thus, the major effects of PGE2 infusion at the site of the periosteum was the formation of primitive woven bone and in muscles the formation of connective tissue.

Animals↗
PubMed1992

Novel approaches with ifosfamide in small cell lung cancer.

During the past 5 years, ifosfamide has been used increasingly in combination chemotherapy for small cell lung cancer (SCLC). The high activity and favorable toxicity spectrum (with the uroprotector mesna) will encourage further use. A policy of no dosage reduction is feasible in patients receiving combination chemotherapy with ifosfamide given as a 24-hour intravenous (IV) infusion, which is much more convenient than the more commonly used 4- to 5-day fractionated regimen. This policy has resulted in actual 2-year survivals of 22% to 33% among SCLC patients not intensively staged. The stability of ifosfamide and its high bioavailability have allowed its use in chronic, 7-day ambulatory IV infusions, with decreased toxicity and hospitalization. Recently, oral and subcutaneous administration also have been tried, again allowing outpatient treatment. The first studies with hemopoietic growth factor support, eg, granulocyte colony-stimulating factor, conducted with combination chemotherapy with ifosfamide-containing regimens in SCLC, demonstrated significant reduction in neutropenia, infections, and antibiotic use. It is clear that the dosage of ifosfamide can be intensified in the future. The broad versatility of the drug will allow interesting new studies, including those to be conducted with outpatients.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1992

Ultrasound evaluation of the common duct in symptomatic and asymptomatic patients.

We studied common duct (CD) diameter using real time ultrasound in 551 patients. The patients were divided into two groups: those referred for evaluation of the biliary tree [biliary-referred group (BRG)], and those referred for a problem unrelated to potential biliary tree pathology [non-biliary-referred group (NBRG)]. Potentially obstructed CDs were excluded from analysis. The CD diameter in the NBRG patients was found to increase after cholecystectomy (p less than 0.0003), but not in patients in this group with intact gallbladders and cholelithiasis. Dilation was observed in the BRG patients with either cholelithiasis (p less than 6 x 10(-7)) or cholecystectomy (p less than 4 x 10(-10)) compared to patients with intact gallbladders without cholelithiasis. To our knowledge, the former phenomenon has not been described in the literature. Our NBRG data suggest that the normal CD diameter should be set at 5 mm and 8 mm, respectively, for patients with intact gallbladders and patients post-cholecystectomy. No correlation was found between duct size and sex, age, or weight.

Adolescent↗
PubMed1991

Diagnostic and genetic studies in 43 patients with classic cystinuria.

We present results for laboratory screening and diagnostic tests--cyanide-nitroprusside test, semi-quantitative thin-layer chromatography, and quantitative amino acid column chromatography--of 43 patients with classic cystinuria. We report the efficaciousness of the cyanide-nitroprusside test and of thin-layer chromatography, as compared with quantitative amino acid chromatography, for detecting heterozygotes for type II or III cystinuria. The quantitative results for aminoaciduria in 57 blood relatives in 23 families were used to categorize the index patients with classic cystinuria. By column chromatography the ranges of excretion rates (mumol/24 h per 1.73 m2 body surface area) of diagnostic amino acids in the index patients were as follows: cystine 556-54044 (normal 20-128), arginine 131-11543 (10-80), lysine 768-21848 (51-514), ornithine 185-5685 (0-80). Also by column chromatography the median values for arginine and ornithine excretion in cystine-lysinuric heterozygotes (among the 57 blood relatives) were significantly higher (P less than 0.01) than in controls but never approached the values for homozygotes. The cyanide-nitroprusside test results were positive in urine samples of 41 of 43 index patients and in 16 (51.6%) of the urine samples of 31 obligate heterozygotes with column chromatographically proven cystine-lysinuria. Thin-layer chromatography detected all of the homozygotes, all the compound heterozygotes, and 54.8% of the carriers. According to the type of aminoaciduria in their relatives, 11 patients with classic cystinuria could be classified as having classic cystinuria type I, 11 as having type II or III, and three as being compound heterozygotes. We discuss the implications of these results for correct diagnoses and for genetic studies in classic cystinuria.

Amino Acids↗
PubMed1990

Comparative pharmacokinetics of escalating doses of doxorubicin in patients with metastatic breast cancer.

Recombinant human granulocyte colony-stimulating factor (G-CSF) has been shown to reduce neutropenia following cytotoxic therapy, thereby enabling dose escalation to improve the response rate. It is important to know whether drug kinetics change as doses are increased. Doxorubicin was selected because of its broad spectrum of activity and its known efficacy in metastatic breast cancer. Doses of 75, 100, 125 and 150 mg/m2 were given to 11 patients with metastatic breast cancer by infusion over 30 min. Serum concentrations of parent drug and metabolites were determined during the first 48 h following the infusion by high-performance liquid chromatography (HPLC). The serum concentration vs time curve decayed as a triple exponential function in four patients and as a double exponential function in seven. A four-compartment model, one central and three peripheral, would predict concentrations to within 1 SE of the observed values. Doxorubicinol was the principal metabolite, and doxorubicinone and 7-deoxydoxorubicinone were clearly identified. There was a linear increase in the AUC infinity with dose. In addition, a small and transient increase in circulating levels of doxorubicinol and other important metabolites was observed 6 h following the administration of doxorubicin, which suggests the existence of an enterohepatic, or other, re-circulation mechanism. We conclude that in the dose range selected the kinetics of doxorubicin are linear and that the increase in toxicities seen with the higher doses of doxorubicin, following the second and third fortnightly administration, may be due to intracellular drug accumulation in tissues.

Adult↗
PubMed1990

Carboplatin in small cell lung cancer.

The high activity of carboplatin as a single agent in small cell lung cancer was first identified in 30 previously untreated patients who had a 60% response, which included a 10% complete remission (CR). In this and subsequent studies, carboplatin showed high activity without the nephrotoxicity and neurotoxicity associated with cisplatin. Gastrointestinal side effects and alopecia were also generally mild; the major toxicity was myelosuppression. Two important studies of carboplatin 300 mg/m2 and etoposide (300 to 400 mg/m2) in divided doses have reported objective responses of 85% (21% CR) and 65% (21% CR) in previously untreated patients. However, the median survival in the first study was only 9.5 months in both limited- and extensive-stage patients. In this study, 19% of patients had substantial dose reductions because of myelosuppression. The second study reported a better median survival of 15.3 months for limited-stage patients and 8.3 months for extensive-stage patients. These patients received a maximum of six courses of chemotherapy as opposed to four in the first study, and cranial irradiation in addition to mediastinal irradiation. There also appeared to be fewer dose reductions, ie, 11% for carboplatin. Another study using the combination of carboplatin and etoposide in extensive-stage patients only reported a 56% response rate, including 16% CR and a median survival of 8.1 months. The major toxicity in these three studies was myelosuppression, particularly leukopenia, but only three neutropenia-associated deaths occurred in a total of 180 patients. A recent study has reported the use of similar doses of carboplatin and etoposide in combination with ifosfamide 5 g/m2 (with mesna) and midcourse vincristine. Thoracic radiotherapy was given after six courses of chemotherapy in responding patients, but no cranial irradiation was used. In 42 patients, 30 of whom had limited-stage disease, the response rate was 78%, including a 57% CR rate. The median survival was 14 months, and the 2-year actual survival rate is 33%. These and other studies of carboplatin combinations (which are only preliminary) have described high response rates and possibly improved survival compared with less intensive therapy.(ABSTRACT TRUNCATED AT 400 WORDS)

Antineoplastic Agents↗