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Biomedical subjects

M Lishner

Publications and source records attributed to M Lishner.

At least 127 records · Page 7Linked to original sources

Late neurological complications after prophylactic cranial irradiation in patients with small-cell lung cancer: the Toronto experience.

We retrospectively analyzed the charts of 58 long-term survivors of small-cell lung cancer (SCLC) (greater than 2 years) for neurological complications and their impact on the well-being of these patients. We also attempted to have patients complete a questionnaire regarding any possible neurological problems. This was done in 14 patients. Metastasis to the CNS occurred significantly less often in patients who received prophylactic cranial irradiation (PCI) in a dose of 20 Gy in five equal fractions (two of 48), compared with patients who did not receive it (four of 10) (P less than .006). Delayed neurological complications occurred in nine of 48 (19%) patients who received PCI. However, in only two patients did PCI appear to be responsible for progressive dementia. In the other seven patients (one with weakness in the arms and legs, one with transient left hemiparesis, two with hearing loss, and three with various visual disturbances), chemotherapeutic agents (mainly cisplatin and vincristine) and underlying diseases probably contributed significantly to the occurrence of these complications. In addition, these neurological disturbances were transient or ran a stable course and did not adversely affect the daily life of these patients. In comparison, amongst the 10 patients who did not receive PCI one had progressive dementia and another had hemiparesis secondary to probable brain embolism. We conclude that the use of PCI in these doses was effective in reducing the frequency of CNS metastases and had an adverse effect on the daily life and well-being only in a minority of the patients. Until results of controlled randomized studies show otherwise, PCI should continue to be used as a part of the combined modality treatment of completely responding patients with limited SCLC.

Aged↗

The effects of leukemia inhibitory factor (LIF) on the blast stem cells of acute myeloblastic leukemia.

Leukemia inhibitory factor (LIF) was tested using three established acute myelocytic leukemia (AML) cell lines. In growth assays in two of the three lines, we found that the addition of LIF increased the doubling time of the clonogenic population but not the total population as assessed by nucleated cell counts. Similarly, tritiated thymidine uptake into total AML populations was not affected by LIF, but the percentage of clonogenic cells killed by exposure to high specific activity 3HTdR was reduced in LIF-treated cultures compared to controls. We interpret these results to indicate that LIF prolongs the cell cycle of stem cells in some AML lines, possibly by increasing the time spent in the G2-M-G1 parts of the cycle. Consistent with this interpretation, we observed a decrease in ara-C sensitivity in LiF treated cultures. Variable results were obtained when freshly obtained AML blasts were exposed to LIF.

Cell Cycle↗

Complications associated with Ommaya reservoirs in patients with cancer. The Princess Margaret Hospital experience and a review of the literature.

The complications associated with the use of Ommaya reservoirs in 106 patients with meningeal involvement due to malignant disease are reviewed. Twenty-seven patients had acute lymphoblastic leukemia, 12 acute myelogenous leukemia, 3 chronic lymphocytic leukemia, 34 lymphoma, 29 carcinoma, and 1 chronic myelocytic leukemia. There were 11 technical complications, including 1 death due to misplacement of the catheter, 2 mild intraventricular hemorrhages, and 5 malfunctioning reservoirs; 3 required craniotomies (1 for subdural hematoma and 2 for subdural hygroma); 13 cases of bacterial meningitis occurred in 10 patients. One patient died of Staphylococcus aureus meningitis. The organisms causing the other infections were mainly coagulase-negative staphylococci (8 cases) or Propionibacterium acnes (2 cases). The projected infection rate for all patients (by Kaplan-Meier analysis) during the first year following insertion of a reservoir was 15%. Successful use of Ommaya reservoirs requires expert surgical implantation and meticulous care during accessing to minimize complications.

Adult↗

Interaction between retinoic acid and cytosine arabinoside affecting the blast cells of acute myeloblastic leukemia.

Retinoic acid (RA) is a potent morphogen that has been shown to increase differentiation in some leukemic cell populations. RA has been used in treatment of some patients with acute myeloblastic leukemia (AML) and myelodysplastic syndromes. In previous experiments we had observed that RA may decrease the self-renewal of blast cells in established cell lines, and in our clinic RA has been tested as maintenance treatment in association with chemotherapeutic drugs. Accordingly, we asked if exposure of AML blast cells to RA affected their subsequent response to ara-C. We found that brief exposure to RA regularly increased the ara-C sensitivity of cells from two established AML cell lines. A similar, though less marked, effect was seen when the blast cells from one patient were tested directly; in a second instance, highly ara-C resistant blasts did not become sensitive when exposed to RA. Experiments using high specific activity tritiated thymidine did not disclose any changes in the proportion of AML cells in the DNA synthesis phase of the cycle at times when their responses to ara-C were changing. We interpret our findings as support for continuing efforts to integrate RA in the management of AML patients and suggest that the mechanism of ara-C sensitization may not depend on changes in the cell cycle.

Cell Survival↗

Spectral analysis of heart rate fluctuations. A non-invasive, sensitive method for the early diagnosis of autonomic neuropathy in diabetes mellitus.

Early detection and a quantitative evaluation of the degree of diabetic autonomic neuropathy were performed in 23 diabetic patients and 22 controls by computerized spectral analysis of beat-to-beat R-R interval variations on a continuous electrocardiogram. Simultaneous recording of cardiac and respiratory activity, R-wave detection by a fast peak detection algorithm and spectrum computation by Fast Fourier transform enabled the study of the power spectrum of heart rate fluctuations. The power of fluctuations at different frequencies is the result of sympathetic and vagal input into the sinoatrial node: this input is derived from vasomotor, baroreceptor and respiratory control loops. A marked reduction in the power of heart rate (HR) fluctuations, at all frequencies, was found in the diabetic patients as compared to controls. This indicates a depression of both parasympathetic and sympathetic activity. The difference was especially pronounced in subjects below age 65. The lowest activity was found in diabetics with concomitant peripheral neuropathy. The method described here is simple, objective, quantitative and very sensitive. It may facilitate the screening of diabetic patients for autonomic neuropathy and enable a convenient quantitative follow-up.

Adult↗

Primary malignant neoplasms associated with chronic lymphocytic leukaemia.

The relationship between chronic lymphocytic leukaemia (CLL) and primary malignant neoplasms was evaluated using data from the Hematology Division in Beilinson Medical Center and the Israel Cancer Registry. The study population consisted of 81 patients diagnosed between 1962 and 1984. A total of 16 patients were found to have 21 malignant neoplasms in addition to their CLL. Excluding patients with nonmelanoma skin tumours, a 1.7 increased risk (statistically not significant) for developing second malignant neoplasms in CLL patients was detected. The only tumour which occurred significantly more than expected subsequent to CLL diagnosis was brain cancer. The coexistence of multiple cancers in the same patient was diagnosed in four of the patients. The results of this study further support the hypothesis that patients with CLL are prone to develop second neoplasms.

Aged↗

Spectral analysis of fluctuations in heart rate: an objective evaluation of autonomic nervous control in chronic renal failure.

A quantitative, noninvasive method of assessing autonomic control, based on the spectral analysis of beat-to-beat fluctuations in heart rate (HR), was applied to patients with chronic renal failure (RF). Since the power spectrum of HR fluctuations measures the dynamic nervous control of HR, it can be used to quantitate a normal control system as opposed to a disturbed or depressed system. Indeed, in RF patients, a strong reduction in the HR power spectrum was observed in all frequency ranges, both sympathetically and parasympathetically mediated. A similar depression in autonomic control was demonstrated in patients on hemodialysis or peritoneal dialysis. RF patients not yet undergoing dialysis show a lesser degree of depression. Spectral analysis of HR fluctuations in RF patients makes it possible to quantitate autonomic dysfunction and to reliably measure its development as a function of time, and requires only a 10-min standard electrocardiogram recording.

Adult↗

Hereditary complement deficiency in survivors of meningococcal disease: high prevalence of C7/C8 deficiency in Sephardic (Moroccan) Jews.

The prevalence of complement deficiency was studied among 111 survivors of sporadic meningococcal disease located through the medical records of 10 Israeli hospitals. There were 11 patients with CH50 = 0: one with systemic lupus erythematosus and 10 with hereditary terminal complement deficiency (four with homozygous C7 and six with C8 deficiency). There was no hereditary complement deficiency among 39 Ashkenazi subjects as against 18 per cent among 38 Sephardi subjects and 40 per cent among 15 of Moroccan ancestry (p less than 0.05). The age at first presentation of meningococcal disease in complement deficient patients was 14.7 +/- 7.6, years compared with 8.1 +/- 10.9 in the non-deficient patients (p less than 0.025). None of the complement deficient patients had meningitis below the age of 5 years vs. 49 per cent of non-deficient subjects. Recurrent meningitis was observed in 40 vs. 4 per cent (p less than 0.01) and meningitis in siblings in 40 vs. 2 per cent respectively (p less than 0.001). In addition to the 10 propositi, 11 non-propositus siblings were identified with severe complement deficiency (six with homozygous C7 and five with C8 deficiency). Seven of the non-propositi had no history at all of meningitis or any other serious systemic disease, underlining the relatively favourable prognosis of terminal complement deficiency. With increasing familiarity with the clinical features of this hereditary disease, it is possible now to identify on clinical grounds patients with meningococcal disease with a high likelihood of terminal complement deficiency.

Adolescent↗

Portal hypertension as an early manifestation of carcinoma of the pancreas.

Massive hematemesis followed by 48 hours the onset of obstructive jaundice in a previously asymptomatic 38-year-old male patient. Splenomegaly was the only abnormal physical finding. Esophagoscopy visualized bleeding varices. The liver scan was normal. Dilated intra- and extrahepatic bile ducts and a possible retroperitoneal mass were demonstrated by ultrasonography. Laparotomy disclosed the presence of a carcinoma of the head and body of the pancreas that obstructed the common bile duct and the portal vein. This case report should draw attention to the vast spectrum of rare presentations of pancreas carcinoma.

Adult↗

Treatment of diabetic perforating ulcers (mal perforant) with local dimethylsulfoxide.

Perforating foot ulcers constitute a major problem in diabetics with peripheral neuropathy for which no specific therapy is available. Twenty patients with chronic, resistant mal perforant were treated by local application of dimethylsulfoxide (DMSO) solution. Complete healing of the ulcers was achieved in 14 patients following 4-15 weeks of daily treatment. Partial resolution was observed in another four patients, and in the remaining two there was no effect. A control group, equal in number, was treated conventionally. Complete healing of the ulcers took place in only two patients. The therapeutic effect of DMSO most probably results from an increase in tissue oxygen saturation via a combined mechanism of local vasodilatation, decreased thrombocyte aggregation, and increased oxygen diffusion. Local DMSO is effective, simple, devoid of systemic side effects, and inexpensive. It should be employed for diabetic foot ulcers prior to the consideration of surgical measures.

Aged↗