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Biomedical subjects

M Rosenfeld

Publications and source records attributed to M Rosenfeld.

At least 73 records · Page 4Linked to original sources

New forms of multidrug therapy for the treatment of leprosy. First report for the practice on rifampicin + sulfamethoxazole-trimethoprim + protionamide and rifampicin + sulfamethoxazole-trimethoprim + isoniazid.

Since 1970, when the lifelong monotherapy with dapsone (DDS) in leprosy could be replaced by short-term combination therapy with rifampicin + isoniazid + protionamide + DDS (Isoprodian-RMP), chemotherapeutic research was faced with two problems: (1) to find alternative treatment regimens for cases of intolerance, and (2) to work out forms of therapy allowing a further reduction of the average treatment time of 2 years. The present paper describes the attempts made to find solutions to these problems. With two new combinations, alternatives have become available, and the average treatment time is shortened to 6 months. Both combinations are also effective in tuberculosis.

Drug Therapy, Combination↗

Integrated complex combinations for the treatment of opportunistic infections in AIDS.

In the present paper the 'serial combinations' (components of the combination offered separately), as used in conventional combination therapy, are compared with the 'integrated complex combination' (offered as fixed combinations). So far, three combinations have been worked out on the basis of this concept (RMP + SMZ + TMP + INH; RMP + SMZ + TMP + PTH; RMP + INH + PTH + DDS). They allow successful treatment of almost all mycobacterial infections and diseases (including tuberculosis and leprosy) and a number of infections caused by gram-negative and gram-positive microorganisms and by Pneumocystis carinii.

Acquired Immunodeficiency Syndrome↗

Ectopic pregnancy: surgical-pathologic correlation with US.

The ultrasound (US) examinations of 53 patients with proved ectopic pregnancy were reviewed and compared with surgical and pathologic findings. The most common finding with US and surgery was free fluid. Hematosalpinx tended to have sharply defined margins, whereas free pelvic hematomas were poorly defined or filled the pelvis. The echogenicity of the clots was variable but generally in the same range of echogenicity as the uterus. A prominent decidual reaction occurred in 26% of the patients and had a variety of appearances.

Adnexal Diseases↗

CT diagnosis of occult incisional hernias.

CT of the abdomen was performed on 14 adult patients 2-25 months after laparotomy in order to evaluate intraabdominal processes. Clinically unsuspected incisional hernias were detected in all cases. These herniations were not disclosed by previous physical examination because of the patients' obesity, abdominal pain, distension, or various other factors. However, CT scans showed the exact size, location, and content of each incisional hernia. The evaluation of postsurgical abdomen by CT should include a careful assessment of previous laparotomy sites in search of occult incisional hernias that may be the source of the patient's abdominal symptoms.

Adult↗

In vitro activity of the new quinoline derivative ciprofloxacin alone and in combination against various Mycobacterium-, Salmonella- and Escherichia coli strains.

The antibacterial effect of 1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-7-piperazine-1-ylquinoline++ + 3-carboxylic acid (ciprofloxacin, Bay o 9867) has been tested using different test systems and various strains, especially of Escherichia coli, Mycobacterium and Salmonella. Ciprofloxacin shows low MIC's against most of the tested strains. The high in vitro and in vivo activity against Salmonella is most promising for cure of salmonellosis.

Anti-Bacterial Agents↗

Improved quality and information in thyroid scintigraphy.

We compared rectilinear scanning, analogous gamma-camera imaging and imaging using a gamma camera interfaced to a computer in order to determine which of these techniques is superior for thyroid scintigraphy. Forty patients with and without goitre and irregular activity distribution were imaged using each of the three techniques. The sets of three scintigrams per patient were rated by seven physicians. These ratings were statistically analysed using a new distribution-free test. Thyroid scintigraphy using a gamma camera interfaced to a computer turned out to be the best method, especially for detecting circumscribed areas of increased uptake. We conclude that this was due to a combination of the following factors: a computer matrix of 128 X 128 pixels in combination with an acquisition zoom of 1.5, the high count density of the scintigrams, computer-controlled documentation after data acquisition and the use of a continuous grey scale for documentation. The improved quality and information content of the scintigrams obtained using a gamma-camera/computer system could improve the diagnostic value of thyroid scintigraphy, especially when the scintigrams are also evaluated quantitatively.

Humans↗

Responsiveness of the in vitro hematopoietic microenvironment to platelet-derived growth factor.

The adherent or stromal cells in human long-term marrow cultures, a possible in vitro counterpart of the in vivo microenvironment, were investigated for responsiveness to platelet-derived growth factor (PDGF). Many stromal cells from cultures derived from normal donors as well as from patients with chronic myelogenous leukemia, bore receptors to PDGF and were stimulated to incorporate [3H]-thymidine by highly purified PDGF and to a lesser extent by epidermal growth factor (EGF). These data suggest that PDGF and perhaps EGF may be involved in the regulation of the in vitro microenvironment and, therefore, of normal and possibly neoplastic hematopoiesis.

Autoradiography↗

Bacterial growth kinetics of Escherichia coli and mycobacteria in the presence of brodimoprim and metioprim alone and in combination with sulfamerazine and dapsone (VI).

Bacterial growth kinetics and checkerboard titration experiments have been performed to determine the inhibitory power of metioprim (I) and brodimoprim (II) alone and in combination with diaminodiphenylsulfone (DDS) using Escherichia coli and mycobacteria as test organisms. The evaluated potency of the new TMP derivatives alone and in combination is compared to TMP and other derivatives. A strongly synergistic activity of I and II in combination with DDS against E. coli and various mycobacteria is observed which is also operative in case of highly DDS-resistant mycobacterial strains. The implication of these findings for the development of a combined chemotherapy with these drugs against atypical mycobacterial infections - especially leprosy - is discussed.

Anti-Bacterial Agents↗

Evidence for selective loss of brain dopamine- and histamine-stimulated adenylate cyclase activities in rabbits with aging.

Dopamine-stimulated adenylate cyclase activity in striatum and both dopamine- and histamine-stimulated adenylate cyclase activity in hypothalamus, frontal cortex and anterior limbic cortex declined by about 50% as rabbits aged from 5.5 months to 5.5 years of age. These changes were primarily in maximal response to amine although an additional component involving decreased affinity in the case of dopamine may also be present. In contrast, dopamine-stimulated adenylate cyclase of retina and both basal and guanyl-5'-yl-imidodiphosphate (Gpp(NH)p)-stimulated activity in these regions were not altered with age. There was no measurable decrease in the old animals in either dopamine or norepinephrine concentration in striatum, anterior limbic cortex or retina, or in choline acetylase activity or [3H]quinuclidinylbenzilate binding in striatum, anterior limbic cortex or frontal cortex. It is proposed that selective age-dependent decreases in transmitter receptors coupled to adenylate cyclases occur in the absence of or independent from neuronal cell loss, as evidenced by the retention of the other biochemical markers.

Adenylyl Cyclases↗

Aging and monoamine receptors in brain.

Biochemical evidence is presented for selective decreases in biogenic amine receptor systems with age in the rabbit. Dopamine-stimulated adenylate cyclase activity in striatum, hypothalamus, frontal cortex, and anterior limbic cortex declined by about 50% as rabbits aged from less than 1 to 5 years of age. Similar decreases were found for histamine-stimulated activity in hypothalamus and the cortical regions. These changes were in maximal response rather than in affinity for amine. In contrast, dopamine-stimulated adenylate cyclase of retina and both basal and Gpp(NH)p-stimulated activity in these regions were not altered with age. In addition, with age the number of binding sites for [3H]spiroperidol, a dopamine antagonist, decreased by 30--40% without change in ligand affinity in striatum and limbic cortex. These changes in striatum and cortex occurred in the absence of decreases in either dopamine concentration or choline acetylase activity. It is proposed that selective age-dependent decreases in the functional number of biogenic amine receptors occur in the absence of, or independent from neuronal cell loss, possibly by a mechanism of desensitization. These changes occurred in brain regions that in man are thought to be of importance in the age-related loss of cerebral function.

Adenylyl Cyclases↗

Biogenic amine-stimulated adenylate cyclase and spiroperidol-binding sites in rabbit brain: evidence for selective loss of receptors with aging.

Evidence for selective decreases in biogenic amine receptor function with age in the rabbit has been obtained. Dopamine-stimulated adenylate cyclase activity in the striatum (caudate-putamen) of rabbit brain declined by about 50 percent as rabbits aged from less than 1 to 4 to 5 years of age. Similar decreases in transmitter-stimulated adenylate cyclase activity were found for histamine as well as for dopamine and norepinephrine in hypothalamus, frontal cortex and anterior limbic cortex. Isoproterenol-stimulated activity was also decreased with age in frontal cortex. These changes appeared to represent decreases in maximal response and not alteration in affinity for amine. In contrast, dopamine-stimulated adenylate cyclase of retina and transmitter-independent (basal or Gpp(NH)p-stimulated) activity in each of the regions studied were not altered with age. Dopamine receptors in striatum directly assessed by measurement of [3H]-spiroperidol binding revealed a comparable decrease in the number of binding sites without change in ligand affinity. Preliminary data also indicated decreased spiroperidol binding sites in the cortical regions of older animals. These changes in striatum and cortex were evident in the absence of decreases in either dopamine content or choline acetylase activity, an activity presumed to be present in neurons containing dopamine receptors. It is proposed that selective age-dependent decreases in postsynaptic biogenic amine receptor content occur in the absence of, or independent from, neuronal cell loss, possibly by a mechanism involving receptor desensitization. These changes occur in the animal model in those brain regions which in man are thought to be of importance in the loss of cerebral function that is found with senscence.

Adenylyl Cyclases↗

Combined therapy in leprosy. Background and findings.

This report is based on data obtained from 64 lepromatous cases. Despite many years of DDS monotherapy, the homogenates from biopsies of these patients revealed 10(4) or more bacteria. From the beginning of combination therapy with synergistic-acting substances (rifampicin + isoprodian (INH + PTH + DDS) the logarithms of the number of bacteria in the homogenates decreased, both during treatment period and during treatment-free observation period (Figs. 3--8). During the whole time biopsies were taken almost monthly. A considerable regression of the bacterial mass or even "negativity" could be observed within a relatively short time. Once started, the process of reduction of bacteria continued also after termination of therapy. To be able to evaluate a medication, therapy-free observation periods (for a minimum of 5 years) are indispensable.

Dapsone↗

Subcellular distribution of [14C]5-hydroxytryptamine in the blood platelets of rabbits: effects of imipramine and and haloperidol.

Long-term (10 days) administration of imipramine [20 mg/(kg X d)] to rabbits significantly increases the Km value (4.0 micron) of 5-hydroxytryptamine uptake in their platelets compared to those of saline- (0.7 micron) or haloperidol- (0.4 micron) treated rabbits. Administration of haloperidol inhibits the 5-hydroxytryptamine uptake non-competitively, and in vitro it had an ID50 value of 22 micron. Intravenous injections of [14C]5-hydroxytryptamine were given to the animals 1 h before blood collection. After isolation of platelets, their sonicates were subjected to 30-60% continuous sucrose gradient centrifugation. The subcellular distribution of [14C]5-hydroxytryptamine indicates that imipramine treatment, in contrast to the control and haloperidol treatment, led to a shift in the exogenous 5-hydroxytryptamine peak from within the granular zone (d 1.18) to the extragranular cytoplasm (d 1.15). Compared to control values, the imipramine treatment caused 63% inhibition in the platelet Na-K-ATPase activity.

Animals↗