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Introduction: Quality indicators (QIs) are widely used tools for antibiotic stewardship programmes. The Access, Watch, Reserve (AWaRe) system has been developed by the WHO to classify antibiotics based on their spectrum of activity and potential selection of antibiotic resistance. This review aimed to identify existing indicators for optimal antibiotic use to inform the development of future AWaRe QIs., Methods: A literature search was performed in PubMed. We included articles describing QIs for hospital and primary healthcare antibiotic use. We extracted information about (i) the type of infection; (ii) setting; (iii) target for quality assessment; and (iv) methodology used for the development. We then identified the indicators that reflected the guidance provided in the AWaRe system., Results: A total of 773 indicators for antibiotic use were identified. The management of health services and/or workers, the consumption of antibiotics, and antibiotic prescribing/dispensing were the principal targets for quality assessment. There was a similar distribution of indicators across primary and secondary care. For infection-specific indicators, about 50% focused on respiratory tract infections. Only a few QIs included information on review treatment or microbiological investigations. Although only 8 (1%) indicators directly cited the AWaRe system in the wording of the indicators, 445 (57.6%) indicators reflected the guidance provided in the AWaRe book., Conclusions: A high number of indicators for appropriate antibiotic use have been developed. However, few are currently based directly on the WHO AWaRe system. There is a clear need to develop globally applicable AWaRe based indicators that can be integrated into antibiotic stewardship programmes., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy.)

Introduction: Over the past 20 years, military medicine made great strides in the medical management of traumatically injured patients. Significant advancements were made in the treatment and rehabilitation after limb loss. These advancements can be attributed to the large number of complex patients presenting to military treatment facilities and the demand for medical professionals to provide care to patients with complex injuries and multiple traumatic amputations. The concern now is to maintain the skills needed to be prepared for the next conflict. To meet this demand, the Extremity Trauma and Amputation Center of Excellence (EACE) initiated the documentation of knowledge, skills, and abilities (KSAs) to ensure that the skill sets needed to treat this unique population are not lost. The EACE developed KSAs to sustain advanced clinical practice for physical therapists, occupational therapists, and prosthetists and is in the process of developing KSAs for orthotists and physical medicine physicians. The learning objectives [terminal and enabling learning objectives (TLOs and ELOs)] derived from each set of KSAs will drive curricula development for enduring education, residencies, and fellowships. This article describes the KSAs and learning objectives for advanced physical therapist competencies in amputation care., Methods: Clinical subject matter experts (SMEs) convened from the Department of Defense (DoD) Advanced Rehabilitation Centers (ARCs) to draft the initial KSAs. All experts had specific expertise in treating individuals with highly complex lower and upper limb amputation. In a quasi-Delphi methodology, the initial draft KSAs underwent five cycles of review and comment by an additional 15 DoD, Veterans Affairs, and civilian institution experts from clinical practice, education, and research. The consensus KSAs were then transcribed into learning objectives with collaboration between clinical subject matter experts and doctoral-level educators., Results: The final program document has 21 instructional modules with 30 TLOs and 157 ELOs., Conclusion: The KSAs and the learning objectives describe the skills expected of an advanced practice physical therapist treating patients with traumatic limb loss. Weaknesses of this document include the focus on traumatic amputation and military specific needs. However, many of the central advanced practices are universal to all physical therapists working in amputation. Thus, this document should serve as a starting point and can evolve to include dysvascular, oncology, and other etiologies. To our knowledge, this is the first paper to describe the KSAs for the advanced practice physical therapist working with traumatic limb loss population. This work will form the framework for physical therapist advanced practice training programs., (Published by Oxford University Press on behalf of the Association of Military Surgeons of the United States 2023. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

Objectives: Peripheral blood smear (PBS) interpretation represents a cornerstone of pathology practice and resident training but has remained largely static for decades. Here, we describe a novel PBS interpretation support tool., Methods: In a mixed-methods quality improvement study, a web-based clinical decision support (CDS) tool to assist pathologists in PBS interpretation, PROSER, was deployed in an academic hospital over a 2-month period in 2022. PROSER interfaced with the hospital system's electronic health record and data warehouse to obtain and display relevant demographic, laboratory, and medication information for patients with pending PBS consults. PROSER used these data along with morphologic findings entered by the pathologist to draft a PBS interpretation using rule-based logic. We evaluated users' perceptions of PROSER with a Likert-type survey., Results: PROSER displayed 46 laboratory values with corresponding reference ranges and abnormal flags, allowed for entry of 14 microscopy findings, and computed 2 calculations based on laboratory values; it composed automated PBS reports using a library of 92 prewritten phrases. Overall, PROSER was well received by residents., Conclusions: In this quality improvement study, we successfully deployed a web-based CDS tool for PBS interpretation. Future work is needed to quantitatively evaluate this intervention's effects on clinical outcomes and resident training., (© American Society for Clinical Pathology, 2023.)

Objectives: Acetaminophen has gained interest in the neonatal community for its use in the management of hemodynamically significant patent ductus arteriosus (HsPDA) in preterm infants. We conducted a systematic review of randomized controlled trials (RCTs) comparing the efficacy and safety of acetaminophen with indomethacin for the management of HsPDA in preterm infants., Methods: We searched PROSPERO, OVID Medline, OVID EMBASE, Wiley Cochrane Library (CDSR and Central), EBSCO CINAHL, and SCOPUS from inception to June 15, 2021. Bibliographies of identified studies were searched for additional references. Data were analyzed with Review Manager (RevMan) Version 5.3., Results: Four RCTs were identified, enrolling a total of 380 subjects. There was no difference between the interventions for the outcome of PDA closure after one course (RR 1.04 [95% CIs: 0.84, 1.29], P -value 0.70) or after two courses of treatment (RR 1.01 [95% CIs: 0.92, 1.12], P -value 0.77); and for the outcome of PDA ligation (RR 1.56 [95% CIs: 0.48, 5.12], P -value 0.46). However, patients who received acetaminophen had lower rates of necrotizing enterocolitis (RR 0.37 [95% CIs: 0.14, 0.95], P -value 0.04). There were no significant differences noted in the other clinical outcomes, that is, intraventricular hemorrhage, bronchopulmonary dysplasia, retinopathy of prematurity requiring treatment, and death. Two studies noted significant post-treatment elevation of serum creatinine and blood urea with indomethacin, as compared to none with acetaminophen use., Conclusions: Acetaminophen has comparable efficacy to indomethacin for the outcome of HsPDA closure, with a better safety profile, that is, lesser rates of necrotizing enterocolitis and post-treatment azotemia noted with its use., Competing Interests: The authors have no conflicts to disclose., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Canadian Paediatric Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The so-called Disability Paradox arises from the apparent tension between the popular view that disability leads to low well-being and the relatively high life-satisfaction reports of disabled people. Our aim in this essay is to make some progress toward dissolving this alleged paradox by exploring the relationship between disability and various "goods of life"-that is, components of a life that typically make a person's life go better for them. We focus on four widely recognized goods of life (happiness, rewarding relationships, knowledge, achievement) and four common types of disability (sensory, mobility, intellectual, and social) and systematically examine the extent to which the four disability types are in principle compatible with obtaining the four goods of life. Our findings suggest that there is a high degree of compatibility. This undermines the widespread view that disabilities, by their very nature, substantially limit a person's ability to access the goods of life, and it provides some guidance on how to dissolve the Disability Paradox., (© The Author(s) 2021. Published by Oxford University Press, on behalf of the Journal of Medicine and Philosophy Inc. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Laboratory medicine, like other areas of medicine, is obliged to adhere to high ethical standards. There are particular ethical issues that are unique to laboratory medicine and other areas in which ethical issues uniquely impact laboratory practice. Despite this, there is variability in ethics education within the profession. This review provides a foundation for the study of ethics within laboratory medicine., Content: The Belmont Report identifies 3 core principles in biomedical ethics: respect for persons (including autonomy), beneficence (and its corollary nonmalfeasance), and justice. These core principles must be adhered to in laboratory medicine. Informed consent is vital to maintain patient autonomy. However, balancing patient autonomy with the desire for beneficence can sometimes be difficult when patients refuse testing or treatment. The use of leftover or banked samples is fundamental to the ability to do research, create reference intervals, and develop new tests, but it creates problems with consent. Advances in genetic testing have created unique ethical issues regarding privacy, incidental findings, and informed consent. As in other professions, the emergence of highly contagious and deadly infectious diseases poses a difficult ethical dilemma of helping patients while protecting healthcare workers., Conclusions: Although many clinical laboratorians do not see or treat patients, they must be held accountable to the highest ethical and professional behavior. Recognition and understanding of ethical issues are essential to ethical practice of laboratory medicine., (© 2019 American Association for Clinical Chemistry.)

Background: This study aimed to describe and to analyse the importance of educational level for controlled risk factors and health-related quality of life (HRQoL)., Methods: This observational study was conducted in nine European countries (5632 patients in 249 practices). We compared patients with a low level of education (up to 9 years) with patients with a high level of education (>9 years), with regard to controlled cardiovascular disease risk factors and HRQoL. A multilevel approach was used for statistical analysis., Results: Patients with a low level of education were older (P < 0.001), more often female (P < 0.001), more often single (P < 0.001) and had a higher number of other conditions (e.g. heart failure) (P < 0.001). Significant differences in terms of controlled risk factors were revealed for blood pressure (RR) ≤ 140/90 mmHg (P = 0.039) and the sum of controlled risk factors (P = 0.027). Higher age, lower education, female gender, living as single, patient group (coronary heart disease patients) and the number of other conditions were negatively associated with HRQoL. A higher sum of controlled risk factors were positively associated with higher HRQoL in the whole sample (r = 0.0086, P < 0.001) as well as in both educational-level groups (r = 0.0075, P = 0.038 in the low-level group and r = 0.0082, P = 0.001 in the high-level group)., Conclusion: Patients with a lower educational level were more often females, singles, had a higher number of other conditions, a higher number of uncontrolled risk factors and a lower HRQoL. However, the higher the control of risk factors was, the higher the HRQoL was overall as well as in both educational-level groups., (© The Author 2013. Published by Oxford University Press on behalf of the European Public Health Association. All rights reserved.)

Background: Cardiovascular prevention can be provided to patients at different risk levels. The aim of this study was to compare the quality of cardiovascular prevention provided in European primary care between patients with diagnosed coronary heart disease (CHD) and individuals at high risk due to known risk factors but not labelled with a diagnosis of cardiovascular disease (CVD). Additionally, we aimed to identify individual and practice factors to predict risk factor control., Methods: An international cross-sectional study was conducted in 10 European countries. Clinical record data were abstracted for quality indicators for 8928 patients in 10 countries and patient questionnaires were completed by 7846 patients in nine countries. Information about 320 general practices was assessed using practice questionnaires and interviews. Hierarchical multilevel modelling was used for analyses., Results: Recording of risk factors and advice was higher in the CHD than in the high-risk group. Risk factor control was better in the CHD group: uncontrolled levels of blood pressure (34.2 vs. 49.3%; p < 0.001), cholesterol (32.4 vs. 64.5%; p < 0.001). Predictors of risk factor control were medication adherence (RR 0.97; p = 0.007) and health-related quality of life (RR 0.86; p = 0.005). Being at high risk (RR 1.42; p < 0.001), being single (RR 1.12; p < 0.001), and having lower educational level (RR 1.09; p < 0.001) were associated with poorer risk factor control. Practice factors were not associated with outcomes., Conclusions: Strategies to improve guidelines adherence in cardiovascular prevention may be stronger focused on individuals at risk before CVD is diagnosed and require organizational and political support to reinforce general practices.

Background: There is emerging evidence that strong primary care achieves better health at lower costs. Although primary care can be measured, in many countries, including Austria, there is little understanding of primary care development., Objective: Assessing the primary care development in Austria., Methods: A primary care assessment tool developed by Barbara Starfield in 1998 was implemented in Austria. This tool defines 15 primary care characteristics and distinguishes between system and practice characteristics. Each characteristic was evaluated by six Austrian primary care experts and rated as 2 (high), 1 (intermediate) or 0 (low) points, respectively, to their primary care strength (maximum score: n = 30)., Results: Austria received 7 out of 30 points; no characteristic was rated as '2' but 8 were rated as '0'. Compared with the 13 previously assessed countries, Austria ranks 10th of 14 countries and is classified as a 'low primary care' country., Conclusion: This study provides the first evidence concerning primary care in Austria, benchmarking it as weak and in need of development. The practicable application of an existing assessment tool can be encouraging for other countries to generate evidence about their primary care system as well.

Background: Detection and registration of high risk for cardiovascular diseases (CVD) by assessing individual's absolute cardiovascular risk is recommended in clinical guidelines. Effective interventions to reduce cardiovascular risk are available, but not optimally implemented. The aim of this study was to assess the quality of cardiovascular risk-factor recording and lifestyle counselling in high-risk patients in European primary care and to identify factors related to these clinical processes., Methods: An international cross-sectional observational study was conducted in stratified samples of primary care practices in nine European countries. Patient records were audited, using a structured data-abstraction tool based on internationally developed quality indicators. To identify factors associated with the recording, additional data were collected in a patient survey. Descriptive and multilevel data analyses were conducted., Results: In 268 general practices across Europe, 3723 records of individuals at high risk for cardiovascular diseases were audited. We found important variations in the quality of documentation of risk factors and lifestyle interventions. Recording of risk factors was best for blood pressure (92.5% of audited records, 95% CI 0.89-0.96). Lifestyle advice was recorded best for smoking cessation (65.6%, 95% CI 0.58-0.73) and worst for physical activity (38.8%, 95% CI 0.31-0.47). Of the study population, 50.6% (0.42-0.59) had elevated blood pressure levels, 59.8% (0.51-0.69) had total cholesterol >5 mmol/l, and 30.5% (0.22-0.39) were smokers. Multivariate analyses showed that recording of risk factors and counselling were related to specific patient characteristics more than to country effects., Conclusions: Analysis of different country results can be helpful for developing quality-improvement strategies.

Background: Topical photodynamic therapy (PDT) is successful in the treatment of nonmelanoma skin cancers and associated precancers, but efficacy is significantly reduced in actinic keratosis lesions not located on the face or scalp., Objectives: To compare the changes in protoporphyrin IX (PpIX) fluorescence in lesions undergoing routine methylaminolevulinate (MAL) PDT and the clinical outcome observed 3 months after treatment in lesions located at acral and nonacral sites., Methods: This study was a noninterventional, nonrandomized, observational study, which monitored changes in PpIX fluorescence in 200 lesions during standard dermatological MAL-PDT. These data were subsequently analysed in terms of lesions located at acral and nonacral sites., Results: Clinical clearance was significantly reduced (P < 0·01) in acral skin lesions when compared with lesions located at nonacral sites. The accumulation and destruction of PpIX fluorescence was significantly reduced in these acral lesions (P < 0·05 and P < 0·001, respectively). Specifically, lesion location at acral sites significantly reduced changes in PpIX fluorescence in actinic keratosis lesions during MAL-PDT (P < 0·01 and P < 0·05)., Conclusions: These data suggest that reduced PpIX accumulation and the subsequent reduction in PpIX photobleaching within acral lesions result in the reduced responsiveness of these lesions to MAL-PDT. Future work should therefore aim to improve photosensitizer accumulation/photobleaching within lesions located at acral sites., (© 2011 The Authors. BJD © 2011 British Association of Dermatologists.)

Background: Photodynamic therapy (PDT) involves the activation of a photosensitizer by visible light to produce activated oxygen species within target cells, resulting in their destruction. Evidence-based guidelines support the efficacy of PDT using topical 5-aminolaevulinic acid (ALA-PDT) in actinic keratoses, Bowen disease and basal cell carcinoma (BCC). Efficacy for nodular BCC appears inferior to that for superficial BCC unless prior debulking or repeat treatments are performed. Objectives The aim of this study was to assess the safety and efficacy of adding a novel iron-chelating agent, CP94 (1,2-diethyl-3-hydroxypyridin-4-one hydrochloride), to topical ALA, to temporarily increase the accumulation of the photosensitizer in the tumour., Methods: A mixed topical formulation of ALA + increasing concentrations of CP94 was used to carry out PDT on previously biopsied nodular BCC with no prior lesion preparation using standard light delivery. The area was assessed clinically and surgically excised 6 weeks later for histological examination., Results: Enhanced PDT using 40% CP94 resulted in significantly greater clearance rates in nodular BCC than with ALA-PDT alone, in our protocol of single-treatment PDT with no lesion preparation., Conclusions: The results of this study demonstrate the safe and effective use of an enhanced ALA-PDT protocol for nodular BCC using CP94, with no adverse reactions to this modification. This is the first time this formulation has been used in patients. This formulation is now the focus of further study.

Background: Photodynamic therapy (PDT) has unique properties which make it suitable for the local treatment of superficial epithelial disorders; it has been suggested as a useful treatment for carcinoma in situ of the vulva., Objectives: To evaluate the effect of the systemic photosensitizing agent meta-tetrahydroxyphenylchlorin (mTHPC or temoporfin; Foscan, Biolitec, Edinburgh, U.K.) in vulval intraepithelial neoplasia type III (VIN III)., Methods: PDT using mTHPC was performed in six patients with VIN III. A dose of 0.1 mg kg(-1) body weight mTHPC was injected intravenously and the area of VIN irradiated 96 h later with 652-nm light from a diode laser. Patients were reviewed 1 week, 6 months and 2 years following treatment., Results: Patients experienced only minimal pain from the initial treatment but two patients subsequently developed severe pain at the treated site for up to 2 weeks following PDT. All patients developed oedema and slough formation at the treated site and one patient developed cellulitis. At 6 months two patients had developed small recurrences of VIN at the original site and one patient had an area of VIN at a new site. These were treated either with further PDT or with a small excision. At 2 years there was no recurrence of VIN at the original site in all patients reviewed., Conclusions: This small case series demonstrates that mTHPC-PDT is a useful initial treatment for VIN III. It is relatively selective, shows good cosmesis and conserves form and function. This is a major advantage over surgery. Repeat treatments are also possible, which is important in a condition such as VIN, which tends to be multifocal. Systemic mTHPC-PDT appears to have an advantage over topical 5-aminolaevulinic acid-PDT as the photosensitizer is distributed widely in areas of disease and consequently identifies foci which may not be apparent clinically but become evident when illuminated.

Objectives: The aim of this study was to compare two different approaches to the measurement of quality in general practice: data derived from routine NHS data sets and results from an index derived from patient-collected data., Methods: A secondary analysis of existing data sets and a cross-sectional survey were carried out in Lothian, Coventry, Oxfordshire and west London. The subjects comprised randomly selected and consenting practices, and a sample of patients within these practices. A National Health Service Practice Performance Index (NHSPPI) was constructed from 16 routinely available NHS performance indicators. The Consultation Quality Index (CQI) combines the Patient Enablement Instrument (PEI) with a measure of how well the patient knew the doctor, and with observed consultation length., Results: Scores for 12 of the 16 indicators varied significantly across the four regions. Mean practice NHSPPI score overall was 21.6 (SD 4.3), which varied significantly across regions. NHSPPI was predicted by practice list size, weighted deprivation index and proportion of other language patients in the practice, although their effects could not be separated. Overall there was no correlation between NHSPPI and CQI, although the prescribing component of the index was positively correlated to mean consultation length and negatively correlated with how well patients knew their doctors., Conclusions: Good quality care as assessed by patients on completion of their consultation is independent of good quality care as assessed by best available measures of practice performance. We suggest that the CQI and the NHSPPI are at least as ready for use as other measures of performance in general practice.

Background: The aim of the study was to assess the face validity of quality indicators being proposed for use in general practice by health authorities., Method: A national survey of health authorities was carried out to identify quality indicators being proposed for use in general practice. A two-stage Delphi process was used to establish general practitioners' (GPs') and health authority managers' views on the face validity of identified indicators. A total of 240 separate indicators identified by health authorities and the NHS Executive as potential markers of the quality of general practice care were assessed. Indicators related to access, organizational performance, preventive care, care for a small number of chronic diseases, prescribing and gatekeeping. The subjects were a purposive sample of 47 health authority managers and 57 general practice course organizers., Results: Thirty-six indicators received median validity scores of 8 or 9 out of a maximum possible score of 9. Of this set, 83 per cent was rated identically by both groups of respondents. Prescribing and gatekeeping indicators generally received low validity scores., Conclusion: Acceptable face valid indicators were identified for all domains except gatekeeping. However, the indicators rated by the sample do not cover all aspects of care. No indicators were proposed for use by health authorities relating to effective communication, care of acute illness, health outcomes or patient evaluation. Although it is possible to develop indicators of general practice care which have face validity in the view of both GPs and managers, these will be very partial measures of quality. In the indicators used in this study, no explicit distinction was made between indicators designed to assess minimum standards with which all practices should comply, and indicators which could be used to reward higher levels of performance. Failure to separate these will result in antagonism from practitioners to quality improvement initiatives in the NHS, and a failure to engage the profession in improving quality of care.

The objective of this multicentre study was to undertake a systematic comparison of face-to-face consultations and teleconsultations performed using low-cost videoconferencing equipment. One hundred and twenty-six patients were enrolled by their general practitioners across three sites. Each patient underwent a teleconsultation with a distant dermatologist followed by a traditional face-to-face consultation with a dermatologist. The main outcome measures were diagnostic concordance rates, management plans and patient and doctor satisfaction. One hundred and fifty-five diagnoses were identified by the face-to-face consultations from the sample of 126 patients. Identical diagnoses were recorded from both types of consultation in 59% of cases. Teledermatology consultations missed a secondary diagnosis in 6% of cases and were unable to make a useful diagnosis in 11% of cases. Wrong diagnoses were made by the teledermatologist in 4% of cases. Dermatologists were able to make a definitive diagnosis by face-to-face consultations in significantly more cases than by teleconsultations (P = 0.001). Where both types of consultation resulted in a single diagnosis there was a high level of agreement (kappa = 0.96, lower 95% confidence limit 0.91-1.00). Overall follow-up rates from both types of consultation were almost identical. Fifty per cent of patients seen could have been managed using a single videoconferenced teleconsultation without any requirement for further specialist intervention. Patients reported high levels of satisfaction with the teleconsultations. General practitioners reported that 75% of the teleconsultations were of educational benefit. This study illustrates the potential of telemedicine to diagnose and manage dermatology cases referred from primary care. Once the problem of image quality has been addressed, further studies will be required to investigate the cost-effectiveness of a teledermatology service and the potential consequences for the provision of dermatological services in the U.K.

Background: Symptoms are an everyday part of most peoples' lives and many people with illness do not consult their doctor. The decision to consult is not based simply on the presence or absence of medical problems. Rather it is based on a complex mix of social and psychological factors., Objectives: This literature review seeks to explore some of the pathways to care and those factors associated with low and high rates of consultation., Methods: The paper examines the impact of socioeconomic and demographic factors on consultation rates and, using a revised version of the Health Belief Model, it highlights the psychological factors which influence decisions to seek medical care. Barriers which can inhibit consultation are discussed, as the decision to seek care will only result in a consultation if there is adequate access to care., Results and Conclusions: Whilst poor health status and social disadvantage increase both "objective" medical need and in turn, consultation rates, a range of other social and psychological factors have been shown to influence consulting behaviour.

The effect of 3 alpha-hydroxy-4-pregnen-3-one (3HP), a Sertoli cell steroid, on spermatogenesis was examined in normal and gonadotropin-suppressed rats, through s.c. as well as direct intratesticular injections. Early experiments employing normal prepubertal male rats indicated that 3HP, when administered at 65 micrograms/100 g BW daily for 15 days, was capable of stimulating pachytene spermatocyte number to 149% of untreated control numbers. It was of interest to determine if this effect could be amplified in gonadotropin-suppressed animals. Neonatally estrogenized rats (500 micrograms estradiol benzoate in 0.1 ml oil at 2 days) were treated on alternate days with 3HP (100 micrograms/100 g BW) for 3 wk, starting at 7 days of age. This treatment significantly increased the number of spermatocytes per tubule cross section from 17.3 +/- 1.9 (in estradiol benzoate-only animals) to 47.1 +/- 7.9 (p less than 0.01). In a similar study, 100 micrograms/100 g BW of testosterone propionate could stimulate spermatocyte number to only 15.1 +/- 2.2 cells per tubule cross section versus estradiol benzoate-only numbers. A single intratesticular injection of 3HP (2 ng in 2.0 microliters oil) in Methallibure-treated rats resulted in a significant increase in late pachytene spermatocyte numbers from 0.77 +/- 0.12 in Methallibure-only-treated rats to 1.70 +/- 0.10 (p less than 0.001) cells per tubule cross section in 28-day-old rats. However, in this study, no other progesterone metabolite or androgenic steroid (testosterone, 5 alpha-dihydrotestosterone, or 5 alpha-androstan-3 alpha, 17 beta-diol) tested was capable of this level of germ cell stimulation. In conclusion, 3HP appears to have a direct effect on germ cell development within the testis at levels much lower than those shown to be effective for androgens. It does not appear that this effect is mediated through the conversion of 3HP to any C21 or C19 steroids, and appears to be the first report of a Sertoli cell steroid with a possible role in the process of mammalian spermatogenesis.

Whey acidic protein (WAP), a hormonally-regulated 14,000 dalton cysteine-rich protein, is the principal whey protein found in rodent milk. Genomic clones encompassing both the 2.8 Kb rat and 3.3 Kb mouse WAP genes have been characterized. The genes consist of four exons and three introns. The middle two exons encode the two cysteine-rich regions which probably form separate protein domains. Homology in the 5' flanking DNA of the mouse and rat extends at least 325 bp upstream of the putative CAP site, including a precisely conserved stretch of 50 bp around the unusual TATA and CAAT sites. The homology previously observed between the 3' noncoding sequences of the rat and mouse mRNAs extends at least 20 bp into the 3' flanking region. Several potential glucocorticoid receptor binding sites have been found in the 5' flanking region of the WAP gene. The conservation of the 5' flanking region of the WAP genes may be related to regulation of expression of WAP by peptide and/or steroid hormones.