Biomedical subjects
Publications and source records attributed to A Horowitz.
A rare occurrence of Warthin's tumour in the parotid glands of three brothers is presented. The only two reports of familial Warthin's tumour are mentioned and pathophysiologic mechanisms are suggested.
Length-tension relations come in two types--the classical type with linearly descending limb, and the "flat," higher type. The classical type, now confirmed in several laboratories, is obtained when sarcomeres are servo-controlled to maintain constant length. The flat type, also confirmed in several laboratories, is obtained in fixed-end contractions, where some sarcomeres have the opportunity to shorten at least slightly. We find that the higher tensions seen in the flat type are indeed the result of very small shortening: when isometric sarcomeres shorten to a slightly shorter (e.g., by 40 nm) length, they go on to produce considerably more isometric tension than if they had remained at the shorter length throughout contraction. We term this phenomenon "shortening-induced tension enhancement." The phenomenon accounts not only for the higher, flatter length-tension relation seen in fixed-end contractions but can explain the creep of tension that occurs in extended tetani. Thus, several issues concerning the interpretation of length-tension relations are resolved by this newly discovered phenomenon.
An experimental study was designed to test the efficacy of a silicon barrier around a nerve root in order to prevent post operative epidural root scar adhesions. In 32 Sprague-Dawley rats a lumbar nerve root was microsurgically exposed bilaterally. In 16 animals a silicon tube, prepared with a longitudinal cut along half of its wall, was placed around one nerve root, while the contralateral side served as control. In another group of 12 animals, an autologous subcutaneous fat graft was placed on the exposed root. A group of 4 animals served as the control group which had not been operated upon. No post operative neurological deficit was observed in any of the animals. All animals were sacrificed 60 days after the operation and a block of tissue including the nerve roots were resected bilaterally without removal of the silicon or fat graft. Longitudinal and transverse cuts of the roots were stained with Haematoxilin and Eosin and with Masson's trichrome collagen stain. The roots in the "unoperated" control group were clean of any scar tissue. In 13 out of 16 animals, silicon prevented scar formation around the root as opposed to scar adhesions around control root on the contralateral side and as compared to unoperated roots. In the silicon group, adhesions penetrated only through the longitudinal narrow cut edge of the tube. Fat did not prevent adhesions in 11 out of 12 animals. We conclude that a silicon barrier is an effective method preventing post operative epidural root scarring in rats.
The higher force observed in fixed-end tetani relative to sarcomere-isometric tetani is commonly attributed to sarcomere length inhomogeneity; sarcomeres in the end regions of the fiber shorten extensively at the expense of the central sarcomeres. By shortening, these sarcomeres supposedly attain higher force production capacity and can thus account for the extra force. However, the fibers could also contain sarcomeres that stay isometric throughout most of the tetanic force plateau. If such sarcomeres undergo slight shortening before their isometric phase, their force-length relation should be elevated (A. Horowitz, H. P. M Wussling, and G. H. Pollack. Biophys. J. 63: 3-17, 1992). These sarcomeres may therefore account for the higher force in fixed-end tetani. To test this possibility, single frog semitendinosus fibers were tetanized under fixed-end conditions. Sarcomere length change during the tetanus was measured at different locations along the fiber by optical diffraction. Fibers stretched to average sarcomere lengths between 2.2 and 3.2 microns contained sarcomeres that, except for some initial shortening during the early part of the tetanus, remained isometric. These sarcomeres were located between the ends and the central region of the fibers. Their force-length relation was higher than the linear force-length relation based on sarcomere length clamps by an average of 14% between sarcomere lengths of 2.4-3.2 microns. Thus slight (1-5%) shortening may explain the relatively higher fixed-end force-length relation.
Anatomical findings as well as theoretical considerations indicate that the myocardial fibers lie along minimal length geodesics of the left ventricular wall. Based upon this knowledge it is shown that the energy spent by the actively contracting fibers during systole, as well as the passive fiber stresses developed through diastole, are minimal in comparison with any other possible fiber configuration. Subsequently, it is concluded that for a given succession of left ventricular states, fiber shortening course and hence the amount of mechanical work are uniquely determined. Comparison with experimental findings concerning global left ventricular systolic work indicates that a given course of afterload produces a unique course of ventricular volume and of mechanical work.
Monoclonal antibodies specific for the rod region can affect smooth muscle myosin's motor properties. Actin movement by phosphorylated myosin was inhibited by an antibody (LMM.4) which binds to the COOH-terminal end of the coiled-coil rod, a region thought to be involved in filament assembly. The actin-activated ATPase activity of the myosin-antibody LMM.4 complex was also reduced 10-fold at actin concentrations that gave maximal turnover rates with filamentous myosin. Metal-shadowing of the phosphorylated myosin-antibody complex at low ionic strength showed small bundles of parallel extended molecules, instead of filaments. Five other anti-rod antibodies had little or no effect on myosin's ability to act as a motor. This is the first demonstration that a muscle myosin's activity is affected by its state of assembly. A common theme that emerges from the studies on both muscle and non-muscle myosins is that assembly into a filamentous structure stimulates the activity of the individual myosin molecules.
We investigated the effect of small shortening imposed on frog muscle fibers during sarcomere-isometric tetani. Sarcomere length was initially kept constant, then slightly shortened (1%-5% of initial length) and clamped again for the remainder of the tetanus. Force level after the shortening was higher than the force level preceding the release. The size of the increase was larger than that predicted by the descending limb of the linear force-length relation. The difference between measured and predicted force levels increased with sarcomere length. At a sarcomere length of 3.2 microns, the force level after the shortening was higher by 50% than the force level expected from the linear descending limb. Dispersion of sarcomere-length within the sampled region was measured by two independent methods: striation imaging and analysis of the intensity profile of the first diffraction order. Sarcomere-length inhomogeneity in the sampled region was too small (standard deviation from the average sarcomere-length was +/- 0.03 microns) to account for the size of the increase in force. We studied the dependence of increase in tetanic force level after small sarcomere-length release on the size, velocity and timing of the release, as well as on initial sarcomere-length. Release size was the major determinant of the amount of increase in force. Release of 20 nm per half sarcomere was sufficient to produce an almost full force increase. Larger releases increased the force only moderately. Over the range studied, release velocity and timing had little or no effect.
Malignant prolactinoma is a rare entity and only a few cases have been published. The diagnostic criteria and the clinical course remain unclear. We present a case of malignant prolactinoma in a woman with a 30-year duration of the disease. In the terminal stage of the disease the prolactinoma metastasized to the left eye, the prolactin level reaching 196000 mU/l. Bromocriptine in high doses was not effective. The response to pergolide was good in the first two years of treatment; thereafter an escape effect was observed. The patient died in a comatose state. A review of previously published cases follows.
A 44-year-old woman with Sjogren's syndrome and mixed cryoglobulinemia developed nodal and pulmonary lymphoma 15 years after the initial diagnosis. The nodal lymphoma was of the composite type and included both monoclonal monocytoid and lymphoplasmacytoid B-cells. The extranodal pulmonary lymphoma included only lymphoplasmacytoid lymphocytes. Complete resolution of the lymphoma was achieved following 3 months of chlorambucil, 5 mg/day, and prednisone, 30 mg/day. Composite lymphoma and monocytoid lymphoma are being encountered more commonly among patients with Sjogren's syndrome. Physicians must therefore become more aware of the existence of both entities.
Phosphorous 31 (31P) nuclear magnetic resonance (NMR) spectra were recorded from perchloric acid extracts of benign and malignant breast tumors. The spectra were correlated with the histopathologic diagnosis and the steroid receptor status of the tumor. Higher relative content of the lipid-derived metabolite glycerolphosphoethanolamine (GPE), the high-energy nucleoside phosphates (nucleoside-diphosphate [NDP], nucleoside-triphosphate [NTP]), and sugar esters of uridine diphosphate (UDPS) appeared in the carcinomas. Malignant tumors also showed a lower ratio of phosphoethanolamine to phosphocholine (PE/PC) than benign conditions. Lower content of the lipid-derived metabolite glycerolphosphocholine (GPC) and high content of the high-energy compound phosphocreatine (PCr) were associated with malignant tumors having high content of estrogen receptors (ER). High PCr content was also associated in the carcinomas with high progesterone receptors (PgR) content. In the benign tumors NDP and NTP were higher in tumors with high PgR content. The authors suggest that 31P magnetic resonance spectroscopy (MRS) of the breast can provide additional variables to diagnose malignancy, and when combined with magnetic resonance imaging (MRI), invasive procedures may be avoided. It also seems that levels of PCr and GPC obtained from the spectra can serve as markers to hormonal receptor status of breast carcinomas, and may be used in addition to the ER and PgR content to improve prediction of the response to hormonal therapy. Additional development requires in situ MRI and MRS combined studies.
We explored personal autonomy issues within family caregiving relationships and found little evidence of significant autonomy conflicts. Findings did suggest, however, that family members were more sensitive to autonomy issues than were their frail older relatives and that both groups defined the disability itself as the major impediment to autonomy in later life. Findings support the usefulness of an expanded definition of autonomy, emphasizing the importance of goal-directed behavior, which may be inhibited by intrinsic conditions as well as external forces.
A six-week-old infant presented with rib trauma and a lung contusion from a nonaccidental compressive chest injury. He developed an illness consistent with diffuse alveolar damage, which worsened over 26 hours. This was complicated by a pneumomediastinum, and the patient recovered with conservative management. The value of isotope bone scanning in addition to x-rays is discussed. Nonaccidental injury should be considered in the differential diagnosis of a pulmonary contusion.
This study compared the size, histology and morphology of coexisting neoplastic polyps found in colonoscopy, and evaluated the clustering of these polyps in patients with either colorectal carcinoma, cancerous polyps or benign adenomas. Patients were divided by their most malignant form of neoplasia: Group A included 58 patients with early invasive cancerous polyps, and Group B included 73 patients with in situ carcinoma within an adenoma. Group C consisted of 335 patients with benign adenomas, and Group D had 289 patients with colorectal carcinoma. There were no significant differences between the four groups regarding sex, age and ethnicity. The cancerous polyps were significantly larger than the benign polyps. There were significantly (P less than 0.01) more patients with multiple (greater than or equal to 5) colonic lesions in Groups A or B than in Groups C or D. Coexisting polyps were much closer to the index growth, and demonstrated more severe dysplastic changes in the case of cancerous polyps than those associated with benign polyps or cancer. Based on our data we speculate that cancerous polyps are not merely a middle link in adenoma-carcinoma sequence, but rather mark a subset of patients who are especially prone to develop neoplastic changes in their colonic mucosa. These patients should be included in a more strict colonoscopic surveillance programme.
Magnetic resonance 1H-imaging and 31P-localized spectroscopy were utilized to monitor, noninvasively, MCF7 human breast cancer tumors implanted in immunodeficient mice. The tumors were followed during estrogen dependent growth and tamoxifen induced remission. Early after tamoxifen administration enhanced necrosis developed, extending to most of the tumor volume. This was followed by growth of repair tissue along with tumor regression. The short-term tamoxifen treatment also modified the content of the phosphate metabolites, increasing the nucleoside triphosphate to inorganic phosphate ratio from 0.41 +/- 0.15 (n = 14) before treatment to 1.10 +/- 0.70 (n = 8, P less than 0.025) and to 1.75 +/- 0.66 (n = 9, P less than 0.0002) 4-7 days and 9-19 days, respectively, after treatment. This change was attributed to the growth of reparative tissue. The results provide new information regarding the response and the mechanism of action of tamoxifen.
Of 6,426 colonoscopies performed in 1978-1987, 66 invasive colorectal adenomatous polyps were removed in 58 examinations. The study group included 36 (62%) men and 22 (38%) women with an age range of 42-96 years. Forty-three patients had invasive pedunculated polyps and 15 had invasive sessile polyps. Following the colonoscopic polypectomy, secondary surgical resection was done in 19 patients with pedunculated polyps and in 13 patients with sessile polyps. The operative specimens showed that the colonoscopic polypectomy removed the entire cancerous focus in all patients with pedunculated polyps, including those with stalk invasion. In contrast, most cases with sessile polyps turned out on operation to be Dukes' B or C carcinoma. Follow-up (mean 4.4 years) was available for 53 (93%) patients: none of 24 unoperated patients with pedunculated polyps suffered from local recurrence. We conclude that colonoscopic polypectomy is sufficient for invasive pedunculated polyps, provided that histology shows that the resection margins are free of tumoral cells. Surgery is recommended for all invasive sessile polyps.
Magnetic resonance imaging has been shown to help in the diagnosis of a glomus tumor in an unusual location in a fingertip. We report a case where magnetic resonance imaging confirmed the presence of a lesion before operation.
Sialadenoma papilliferum is a rare, benign exophytic tumour of salivary glands. The preferred site of this tumour is usually the hard palate. A case of sialadenoma papilliferum occurring in the parotid gland of a 49-year-old man is presented; only one such case has been previously described.
We examined the consequences of incident self-reported vision loss among a cohort of community-living people aged 66 years and older. Those with visual decline were older than those reporting constant excellent or good vision, but not different in any other demographic characteristic, the use of formal support services, the use of health services, or ADL (activities of daily living) functioning. Controlling for age and sex, vision loss was associated with unmet instrumental ADL needs such as housekeeping, grocery shopping, and food preparation, and with physical and emotional disabilities. We discuss the implications of these disabilities in terms of the challenges to the aging and blindness service delivery systems.