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Biomedical subjects

K Cooper

Publications and source records attributed to K Cooper.

At least 37 records · Page 2Linked to original sources
PubMed1991

In situ human papillomavirus (HPV) genotyping of cervical intraepithelial neoplasia in South African and British patients: evidence for putative HPV integration in vivo.

In South Africa asymptomatic wart virus infection diagnosed by morphological criteria occurs in 16-20% of all ethnic groups; the incidence in black women is 66%. To identify human papillomavirus (HPV) types the prevalence of HPV in cervical intraepithelial neoplasia (CIN) in South African women (n = 72) with age matched British women (n = 73) was compared by non-isotopic in situ hybridisation (NISH) using digoxigenin labelled probes for HPV 6, 11, 16, 18, 31, 33 and 35 on archival biopsy specimens. A higher proportion of British biopsy specimens (68%) contained HPV than those from South Africa (50%) in CIN 2 and 3; this difference was due to HPV 16. Thirty six per cent of the positive biopsy specimens from South African women also contained HPV 33/35 compared with 16% in the United Kingdom. There was no difference in HPV detection with age in either group. These data indicate that HPV types vary geographically, with "minor" HPV types being more common in South Africa. Three qualitatively distinct NISH signals were observed; a diffuse (type 1) signal in superficial cells, mainly koilocytes; a punctate signal (type 2) in basal/"undifferentiated" cells in CIN 3; and combined type 1 and 2 signals in CIN with wart virus infection (type 3). The punctate signal may represent HPV integration.

Adolescent↗
PubMed1991

In situ evidence for HPV 16, 18, 33 integration in cervical squamous cell cancer in Britain and South Africa.

In a previous study three types of HPV signal were described in CIN. It was suggested that a type 1 signal represented episomal HPV while a type 2 signal represented integrated HPV; and a type 3 signal was indicative of both episomal and integrated HPV. To test this hypothesis 91 squamous cell cancers (SCC) of the cervix from Britain and South Africa were examined for HPV 6, 11, 16, 18, 31, 33, 35. Of the South African group (n = 69) 64% contained HPV types 16 (n = 29) and 18 (n = 15). The SCC in the British group (n = 22) contained HPV 16 and HPV 33 in 12 and three cases, respectively. Of the HPV positive biopsy specimens, 86% showed a type 2 signal in keratinising and non-keratinising tumours and the remainder a type 3 signal. Type 3 signal was present only in keratinising tumours. The presence of punctate signal in 100% of HPV containing SCC, together with localisation of HPV signal to sister chromatids in tumour cell mitotic figures in vivo, provides further evidence for type 2, and the punctate component of type 3 signal representing viral integration.

Age Factors↗
PubMed1991

Wernicke's encephalopathy and alcohol-related disease.

A pilot study of 31 consecutive alcohol-related deaths over an 8-month period revealed the presence of histologically diagnosed Wernicke's encephalopathy in 17 cases. Analysis of the clinical records revealed that a disturbance of the mental state was the commonest finding and neurological signs were present in only 2 of the 17 cases (ataxia 1, peripheral neuropathy 1). Analysis of 22 ward admissions for Wernicke's encephalopathy during the same 8-month period revealed that the diagnosis is easily made when neurological deficits (ophthalmoplegia, ataxia) accompany mental changes and when Wernicke's encephalopathy is the predominant illness. In patients with established alcohol-related disease attention is often directed to the presenting illness so that Wernicke's encephalopathy may easily be overlooked as a cause of deterioration in the mental state in these patients. It is recommended that routine management of patients with alcohol-related disease should include thiamine even if neurological signs are absent.

Adult↗
PubMed1991

Basic medical physiology: the whole is more than the sum of its parts.

In this article we examine the role of basic medical physiology in medical school education. We discuss the historical background, courses in this subject, and methods of teaching it. We conclude that the teaching of medical physiology should emphasize the study of organ systems and of the intact body. The techniques should emphasize meticulous observation, the posing of hypotheses, and the subsequent testing of the hypotheses, i.e., the use of the method used successfully in research. Students should learn the power of the experimental approach and to appreciate the immense variability possible in responses in complex organisms. They should also learn that principles of statistical probability applied logically can detect important differences in data that may be obscured by this variability. They should learn that there are no rigid answers when studying an individual and that they must continue to learn throughout their lives.

Animals↗
PubMed1991

Inwardly rectifying potassium current in mammalian lens epithelial cells.

Lens potassium conductance is essential for the maintenance of lens volume and transparency. Recent work has identified three major potassium currents in lens: 1) an outwardly rectifying current, 2) an inwardly rectifying current, and 3) a calcium-activated current. This paper presents a study of the lens inward rectifier using whole cell and single-channel patch-clamp techniques. Inwardly rectifying potassium current is present in isolated human, rabbit, rat, and mouse lens epithelia. The voltage about which rectification occurs depends on the external potassium concentration. Internal magnesium is not necessary for rectification. In physiological saline, a time-dependent decrease in current during sustained hyperpolarization is seen. This "droop" is due to voltage-dependent block by external sodium. The inward rectifier is also effectively blocked by external cesium or barium but not by tetraethylammonium or 4-aminopyridine. The mouse lens inward rectifier has a single-channel conductance of 32 pS (measured on-cell with 150 mM potassium in the pipette). The single-channel current-voltage relationship is linear in the inward direction. In contrast to the macroscopic case, no outward current was measurable. The inward rectifier in lens has the necessary properties to be involved in setting resting voltage.

Animals↗
PubMed1991

Cardiopulmonary resuscitation and the patient with cancer.

The records of 114 cancer patients suffering cardiopulmonary arrests (CPA) during a 3-year period at Memorial Sloan-Kettering Cancer Center (MSKCC) were retrospectively reviewed to identify variables predicting final outcome in these patients. Although 65.7% of the patients were successfully resuscitated, only 12 (10.5%) were discharged alive from the hospital. Median survival after discharge was 150 days. By univariate and multivariate analysis, the only variable predicting the likelihood of a patient's being discharged alive after a CPA was the performance status of the patient at the time of admission to the hospital. Thus, a patient spending more than 50% of the time in bed at the time of admission had only a 2.3% chance of being discharged alive after CPA. A thorough discussion of these findings between physicians and patients and their families is strongly recommended at the time of admission to spare cancer patients unnecessary invasive resuscitative procedures.

Female↗
PubMed1990

The role of ifosfamide plus cisplatin-based chemotherapy as salvage therapy for patients with refractory germ cell tumors.

A prospective study of four cycles of etoposide with ifosfamide and cisplatin (VIP) chemotherapy was conducted in 42 germ cell tumor (GCT) patients who were refractory to cisplatin with etoposide/vinblastine-based therapy. Forty patients were evaluable for response. Ten patients (25%) had a complete response: seven to chemotherapy alone and an additional three patients after surgical resection of viable GCT. With a median follow-up of 15 months, four complete responders relapsed, and six patients (15%) remain in remission. Hematologic and nephrotoxicity were moderately severe. Durable complete responses with VIP as second salvage were achieved and suggests that ifosfamide adds efficacy to standard first-salvage therapy. The observed nephrotoxicity and myelotoxicity are considerations in the design of ifosfamide-cisplatin-based regimens. Hematopoietic growth factors may be useful in ameliorating myelotoxicity. The early use of ifosfamide-based chemotherapy may reduce the nephrotoxicity exacerbated by prior cisplatin. A trial of VIP as first salvage after a relapse from a complete response to platinum-based induction therapy is warranted. The modest proportion of patients who achieve a durable remission to VIP as second salvage emphasizes the need for more efficacious salvage therapy for patients who do not achieve a durable complete response.

Adolescent↗
PubMed1990

Kaposi's sarcoma associated with acquired immunodeficiency syndrome presenting as a vulval papilloma. A case report.

A patient with acquired immunodeficiency syndrome (AIDS)-associated Kaposi's sarcoma presenting with a vulval neoplasm is reported. Although more common in black than white people, Kaposi's sarcoma infrequently presents with gynaecological symptoms or lesions. In this case report the management of Kaposi's sarcoma presenting as a vulval neoplasm in a young woman with a positive antibody test to HIV is discussed and the need to screen young women with vulval neoplasms for this infection is highlighted.

Adult↗
PubMed1990

Carboplatin, etoposide, and bleomycin for patients with poor-risk germ cell tumors.

A prospective study of four cycles of carboplatin (CBDCA) + etoposide + bleomycin (EBC) was conducted in 32 previously poor-risk nonseminomatous germ cell tumor (GCT) patients and the results compared with past studies. Patients with extragonadal (nine patients) and testicular nonseminomatous GCT with a probability of complete response (CR) less than 0.5 as calculated by a mathematical model using marker values and number of metastatic sites (23 patients) were included. Nineteen patients (59%) achieved a CR and 14 complete responders (43%) remain free of disease. The overall and durable CR proportions were similar to those observed in prior poor-risk studies at Memorial Sloan-Kettering Cancer Center. Myelosuppression was the major toxicity. Based on the low CR proportion, EBC is no better than other standard programs for poor-risk GCT. However, its ease of administration as an outpatient, mild renal and gastrointestinal toxicity, and efficacy comparable to cisplatin-based chemotherapy used in prior poor-risk trials at Memorial Sloan-Kettering Cancer Center warrant a Phase III trial comparing CBDCA-based and cisplatin-based chemotherapy for good-risk GCT patients.

Adolescent↗
PubMed1990

Use of immunotoxins in combination to inhibit clonogenic growth of human breast carcinoma cells.

Substantial heterogeneity has been observed in the expression of individual antigens within tumor cell populations. Immunotoxins which bind to different cell surface antigens might exert additive or synergistic cytotoxicity when used in combination to eliminate all clonogenic cells within a tumor. Immunotoxins have been prepared by conjugating recombinantly derived toxin A chain to different monoclonal reagents which recognize cell surface determinants of Mr 42,000 (317G5), 55,000 (260F9), and 200,000 (741F8). Each immunotoxin was evaluated for binding, internalization, and cytotoxicity with four breast cancer cell lines. Each of the three immunotoxins bound to the SKBr3 cell line and exerted antitumor activity in a limiting dilution clonogenic assay. Simultaneous treatment with two immunotoxins produced additive antitumor activity with each of the possible combinations. Additive binding could be demonstrated by immunofluorescent techniques, however, with only one of three combinations. With two of the three combinations, subpopulations of tumor cells could be identified which lacked one or the other antigenic determinant but not both. Consequently, log-additive antitumor activity was produced by immunotoxins in combination, and heterogeneity of antigenic targets may have contributed to the combined cytotoxicity in some but not all cases.

Antibodies, Monoclonal↗
PubMed1990

The effect of a brain lesion on bone healing.

Using a feline model, the effects of stereotaxic brain lesions producing unilateral spasticity on bilateral fibular osteotomies were observed. Healing in spastic limbs occurred with more new bone formation than on the contralateral (control) side. Union appeared to be slightly faster in spastic limbs. Histomorphometric analysis of resected fibular specimens following union revealed little difference between spastic and non-spastic limbs. When these brain-lesioned animals were compared with a group with identical osteotomies but no brain lesions in respect of various systemic biochemical and endocrine parameters, no differences were found.

Animals↗
PubMed1990

Adenomatous hyperplasia of the rete testis in the undescended testis.

Multiple foci of micronodular or tubulopapillary structures were noted in the rete testis of 13 cases of undescended testes. These structures were lined by low columnar to cuboidal epithelium, showed back-to-back crowding, and were supported by a thin lamina propria. These changes, referred to as adenomatous hyperplasia of the rete testis, appear to be a frequent finding in the undescended testis. An age-matched control group did not show any of these features.

Adolescent↗
PubMed1990

Decompression of epidural metastases from germ cell tumors with chemotherapy.

Epidural cord compression from germ cell tumor metastases is not common. Treatment usually requires high dose corticosteroids with radiation therapy and/or surgical decompression. Three patients with epidural germ cell tumor metastases were treated with cisplatin-based chemotherapy and all three had complete neurologic recovery. Systemic chemotherapy should be considered as initial therapy with corticosteroids for epidural cord compression from metastatic germ cell tumor.

Adult↗
PubMed1990

Magnetic resonance appearance of sacral insufficiency fractures.

Insufficiency fractures of the sacrum are a commonly recognized form of stress fracture typically occurring in elderly patients. As such patients usually present with low back pain, MR imaging is often performed initially as a means of evaluation. We present 5 patients with sacral insufficiency fractures imaged with MR. Metastatic disease was a leading clinical suspicion as all patients were elderly and three had known primary neoplasms. T1-weighted sequences demonstrated bands of decreased signal intensity, usually paralleling the sacral aspect of the sacroiliac joints and occasionally occurring as a horizontal band across the sacral body. Four of five patients underwent further evaluation with computed tomography (CT) or nuclear bone scanning, which confirmed the diagnosis of sacral insufficiency fracture. We conclude that MRI is sensitive but not specific in detecting sacral insufficiency fractures. As MR imaging is rapidly becoming the method of choice for evaluating back pain, it is important to consider this diagnosis in elderly persons.

Aged↗
PubMed1990

Electrophysiology of cultured human lens epithelial cells.

The lens epithelial K+ conductance plays a key role in maintaining the lens ionic steady state. The specific channels responsible for this conductance are unknown. We used cultured lens epithelia and patch-clamp technology to address this problem. Human lens epithelial explants were cultured and after 1-4 passages were dissociated and used in this study. The cells from which we measured had a mean diameter of 31 +/- 1 microns (SEM, n = 26). The resting voltage was -19 +/- 4 mV (SEM, n = 10) and the input resistance was 2.5 +/- 0.5 G omega (SEM, n = 17) at -60 mV. Two currents were prominent in whole-cell recordings. An outwardly rectifying current was seen in nearly every cell. The magnitude of this current was a function of K+ concentration and was blocked by 3 mM tetraethylammonium. The instantaneous current-voltage relationship was linear in symmetric K+, implying that the outward rectification was due to gating. The current showed complex activation and inactivation kinetics. The second current seen was a transient inward current. This current had kinetics very similar to the traditional Na+ current of excitable cells and was blocked by 0.1 microM tetrodotoxin. In single-channel recordings, a 150-pS K+ channel and a 35-pS nonselective cation channel were seen but neither account for the macroscopic currents measured.

Adult↗
PubMed1990

Potassium channel in rabbit corneal endothelium activated by external anions.

The apical membrane of the rabbit corneal endothelium contains a potassium-selective ionic channel. In patch-clamp recordings, the probability of finding the channel in the open state (Po) depends on the presence of either HCO3- or Cl- in the bathing medium. In a methane sulfonate-containing bath, Po is less than 0.05 at all physiologically relevant transmembrane voltages. With 0 mM [HCO3-]o at +60 mV, Po was 0.085 and increased to 0.40 when [HCO3-]o was 15 mM. With 4 mM [Cl-]o at +60 mV, Po was 0.083 and with 150 mM Cl-, Po increased to 0.36. Low Po's are also found when propionate, sulphate, bromide, and nitrate are the primary bath anions. The mechanism of action of the anion-stimulated K+ channel gating is not yet known, but a direct action of pH seems unlikely. The alkalinization of cytoplasm associated with the addition of 10 mM (NH4)2SO4 to the bath and the acidification accompanying its removal do not result in channel activation nor does the use of Nigericin to equilibrate intracellular pH with that of the bath over the pH range of 6.8 to 7.8. Channel gating also is not affected by bathing the internal surface of the patch with cAMP, cGMP, GTP-gamma-s, Mg2+ or ATP. Blockers of Na/H+ exchange, Na(+)-HCO3- cotransport, Na(+)-K+ ATPase and carbonic anhydrase do not block the HCO3- stimulation of Po. Several of the properties of the channel could explain some of the previously reported voltage changes that occur in corneal endothelial cells stimulated by extracellular anions.

Animals↗
PubMed1990

New techniques for the study of lens electrophysiology.

The development of the gigohm seal patch clamp has extended the use of the voltage clamp technique to cells too small to study with more conventional approaches. We report the application of this technique, in its many configurations, to the study of lens epithelial cells. The technique allows measurement of membrane current at the microscopic (single channel) level or at the macroscopic (whole cell) level. At the single channel level, three configurations (on-cell, inside-out, and outside-out) are standard. The advantages and disadvantages of each are discussed. A more novel configuration, the on-cell whole-cell configuration, has several advantages over these more traditional patch configurations. Measurement of current from the entire cell membrane under voltage clamp can be achieved with the whole cell variant of the patch clamp technique. Two less invasive versions of this procedure (the perforated patch technique and droop analysis) are presented. Finally, the extension of the whole cell technique to a pair of dissociated cells is shown to allow the measurement of currents flowing through gap junctions. For each case, data is presented from lens epithelial cells (from frog, chick, rabbit and human).

Animals↗